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Crossroads in the combined-modality management of gastroesophageal junction carcinomas.

ABSTRACT: An epidemiologic shift in esophageal and gastric carcinomas has occurred in recent years in the Western world. Adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is now the predominant esophageal carcinoma, and proximal gastric cancers now account for nearly half of gastric carcinomas. Tumors involving the GEJ appear to be a distinct clinical entity that presents a challenge to oncologists due to issues in staging and classification and uncertainties regarding optimal treatment approach. Beyond surgical resection as the primary treatment modality, the roles of neoadjuvant or adjuvant therapies in GEJ cancers are not clearly defined. This article reviews the major randomized trials of combined-modality treatment in populations with esophageal and gastric cancers that included patients with GEJ carcinomas and discusses how the findings relate to and inform the management of GEJ tumors. In general, preoperative or perioperative chemotherapy appears to improve survival, and the addition of neoadjuvant or adjuvant chemoradiotherapy increases locoregional control and appears to improve survival. Although GEJ tumors account for only 20% to 35% of cancers in the most relevant randomized trials, the available data suggest that trimodality therapy with chemotherapy, radiation, and surgery is a reasonable treatment approach for GEJ tumors. Further clinical trials are needed to define the optimal sequencing and combinations of surgery, radiotherapy, and chemotherapy. These trials should include appropriate definitions and stratification of GEJ tumors in order to facilitate translation of findings to treatment practice.

SUBMITTER: Apisarnthanarax S

PROVIDER: S-EPMC2632556 | biostudies-other | 2008 Sep

REPOSITORIES: biostudies-other

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Crossroads in the combined-modality management of gastroesophageal junction carcinomas.

Apisarnthanarax Smith S Tepper Joel E JE

Gastrointestinal cancer research : GCR 20080901 5

An epidemiologic shift in esophageal and gastric carcinomas has occurred in recent years in the Western world. Adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is now the predominant esophageal carcinoma, and proximal gastric cancers now account for nearly half of gastric carcinomas. Tumors involving the GEJ appear to be a distinct clinical entity that presents a challenge to oncologists due to issues in staging and classification and uncertainties regarding optimal tre ...[more]

PMID: 19259307

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Project description:BackgroundAdenocarcinomas of both the gastroesophageal junction and stomach are molecularly complex, but differ with respect to epidemiology, etiology and survival. There are few data directly comparing the frequencies of single nucleotide mutations in cancer-related genes between the two sites. Sequencing of targeted gene panels may be useful in uncovering multiple genomic aberrations using a single test.MethodsDNA from 92 gastroesophageal junction and 75 gastric adenocarcinoma resection specimens was extracted from formalin-fixed paraffin-embedded tissue. Targeted deep sequencing of 46 cancer-related genes was performed through emulsion PCR followed by semiconductor-based sequencing. Gastroesophageal junction and gastric carcinomas were contrasted with respect to mutational profiles, immunohistochemistry and in situ hybridization, as well as corresponding clinicopathologic data.ResultsGastroesophageal junction carcinomas were associated with younger age, more frequent intestinal-type histology, more frequent p53 overexpression, and worse disease-free survival on multivariable analysis. Among all cases, 145 mutations were detected in 31 genes. TP53 mutations were the most common abnormality detected, and were more common in gastroesophageal junction carcinomas (42% vs. 27%, p = 0.036). Mutations in the Wnt pathway components APC and CTNNB1 were more common among gastric carcinomas (16% vs. 3%, p = 0.006), and gastric carcinomas were more likely to have ≥3 driver mutations detected (11% vs. 2%, p = 0.044). Twenty percent of cases had potentially actionable mutations identified. R132H and R132C missense mutations in the IDH1 gene were observed, and are the first reported mutations of their kind in gastric carcinoma.ConclusionsPanel sequencing of routine pathology material can yield mutational information on several driver genes, including some for which targeted therapies are available. Differing rates of mutations and clinicopathologic differences support a distinction between adenocarcinomas that arise in the gastroesophageal junction and those that arise in the stomach proper.

Dataset Information

Crossroads in the combined-modality management of gastroesophageal junction carcinomas.

Publications

Crossroads in the combined-modality management of gastroesophageal junction carcinomas.

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