Should Genomic Profiling Be Routine in Esophagogastric Cancer?

Yelena Janjigian, MD, Memorial Sloan Kettering Cancer Center, and Howard Hochster, MD, Rutgers Cancer Institute of New Jersey, offered varying opinions on whether routine genomic profiling should be performed in esophageal cancers at the Great Debates and Updates in Gastrointestinal Cancer Conference (March 24, 2018; New York, NY).

Dr Janjigian argued in favor of routine genomic profiling for esophageal cancer stating, “genomic profiling is already routine in esophageal cancer and if you aren’t using it, you are dated.”

The genomic spectrum for esophageal squamous cell cancer has been laid out by The Cancer Genome Atlas and has four distinct subtypes—gastroesophageal adenocarcinomas with Chromosomal Instability (CIN), gastric adenocarcinomas with EBV Infection (EBV), Gastric adenocarcinomas with microsatellite instability (MSI), and gastric adenocarcinomas with genomic stability (GS).

Up to 50 percent of EG tumors have potentially targetable alterations, including ERBB2 and MSI. Many of the tumors have three or more alterations that require more than one form therapy, making routine genomic profiling important for overall treatment and survival of patients, argued Dr Janjigian.

In her concluding remarks, Dr Janjigian spoke of the advantages associated with routine genomic profiling in esophagogastric cancer such as efficiency and cost-effectiveness, genetic predict response to targeted therapy, stratification of HER2+ tumors, identification of MSI-H, EBV, and high mutational burden tumors, facilitation of ctDNA detection, Germline analysis CDH1, ATM, BRCA, and its advantages to research and discovery.

Dr Hochster gave his argument next, stating that next-generation sequencing (NGS) should not be routine in gastroesophageal cancer.

“The utility of NGS depends not only on being able to describe the mutations, but whether you have a treatment for them,” stated Dr Hochster during his argument. He provided overviews of studies in which data from routine genomic testing in over half of the patients showed no actionable mutations. He explained that because NGS gives few actionable mutations, it causes extra unnecessary work than other methods of testing.

Dr Hochster concluded his argument by stating that NGS gives few actionable mutations and the most important factors for treatment are HER2 amplification, MSI status, and EBV, all of which do not require NGS. “Testing for these factors can be done by IHC and FISH at lower cost and should be the standard for now,” he stated.—Janelle Bradley

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