The first study to compare molecular landscapes of early onset and late onset appendiceal cancer has revealed distinct non-silent mutations in the tumors of younger patients. Published in JAMA Network Open, the study sets the stage for the development of potential therapeutic advances for this rare disease.
“Appendiceal cancer among young patients harbors a distinct biology, which has potential clinical actionability,” said Andreana Holowatyj, Ph.D., an assistant professor of medicine and cancer biology at Vanderbilt University Medical Center. Holowatyj and Xingyi Guo, Ph.D., assistant professor of medicine at Vanderbilt, are co-corresponding authors of the study.
“Appendiceal cancer among young patients harbors a distinct biology, which has potential clinical actionability.”
Analyzing Genomic Profiles
Using data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) consortium, Holowatyj and colleagues analyzed tumor genomic profiles of 109 early onset appendiceal cancer cases (under 50 years of age) and 276 late onset cases (age 50 and older).
Compared to patients with late onset appendiceal cancer, patients with early onset disease had higher odds of presenting with non-silent mutations in PIK3CA, SMAD3 and TSC2 and lower odds of presenting with non-silent mutations in GNAS.
“There are currently no targeted therapies specifically for appendiceal cancer patients,” Holowatyj said. “After surgery, NCCN guidelines recommend to treat it as a right-sided colon tumor for that reason. But the fact that one of every eight young patients diagnosed with appendiceal cancer has a PIK3CA mutation – a much higher mutation rate compared with late-onset cases – really lends for the potential and the promise to evaluate repurposing existing drugs for early onset patients diagnosed with this rare malignancy.”
A targeted therapy for the PIK3CA mutation when it occurs in advanced breast cancer, alpelisib, has already been approved by the U.S. Food and Drug Administration.
Demographic and Clinical Patterns
The study also shed light on demographic and clinical patterns of early onset appendiceal cancer. Non-Hispanic Black patients accounted for a larger proportion of early onset cases (8.3 percent) versus late onset cases (4 percent). However, histological subtype did not significantly differ by age of disease onset.
“This study also showed that, in contrast to colorectal cancer where one out of every 10 adults are diagnosed before age 50, one out of every three adults with appendiceal cancer are diagnosed before age 50,” Holowatyj said.
“Given its increasing incidence, especially among young people, it merits further investigation.”
Future Research
Although appendiceal cancer is rare, its incidence is on the rise. Cancer of the appendix is typically found during surgery for acute appendicitis, and even though the rate of appendectomies has been stable over the last two decades, diagnoses have increased 232 percent in the United States.
“As a rare disease, appendiceal cancer is understudied, and it is challenging to garner sufficient resources and funding to study this malignancy,” Holowatyj said. “But given its increasing incidence, especially among young people, it merits further investigation.”
