The same chemotherapy used for colon cancer is also used for cancer of the appendix, which is part of the colon, but this approach has proven to be largely ineffective. Now, gene expression profiling for appendiceal cancer has demonstrated that the disease is, in fact, quite distinct from colorectal cancer, and may require different treatment.

A rare malignancy affecting approximately 2,500 people per year in the United States, cancer of the appendix has the propensity to metastasize throughout the peritoneal cavity. Peritoneal metastases from appendiceal cancer and from colon cancer are both addressed with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC, in which heated chemotherapy is placed directly into the abdominal cavity at the time of surgery).

This approach shows great promise, according to Edward A. Levine, MD, chief of the surgical oncology service at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, and coauthor of the gene expression profiling study, published in Journal of the American College of Surgeons. However, many HIPEC patients experience cancer recurrence.

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In order to better predict oncologic outcomes, Levine and colleagues analyzed global gene expression in 41 tissue samples of peritoneal metastases (26 appendiceal and 15 colorectal) taken from persons undergoing HIPEC with complete cytoreduction and more than 3 years of follow-up. They found three distinct phenotypes, two of which consisted of predominantly low-grade appendiceal samples and one consisting of predominantly colorectal samples. Genetic signatures predicted survival of low-risk vs high-risk appendiceal cancer and low-risk appendiceal cancer vs colon primary cancer.

Having confirmed the unique biology of appendiceal cancer, Levine’s team suggested that basing treatment for such lesions on colon cancer regimens may be unwarranted, and that a fresh therapeutic approach to cancer of the appendix is needed. The newly identified phenotypes could lead to more effective treatments for both diseases.