IU research leads to risk factor test for rare chest cancers

By Kevin Fryling

Research conducted by physicians and scientists at the Indiana University School of Medicine has resulted in a genetic test to predict the risk of recurrence of thymoma, a rare tumor of the upper chest. The study results were presented in a poster presentation at the 2012 American Society of Clinical Oncology Annual Meeting in Chicago.

Sunil Badve, M.B.B.S., M.D., Yesim Gökmen-Polar, Ph.D., and Patrick Loehrer Sr., M.D., pinpointed 19 genes that appear to forecast the chance that thymoma patients will develop a second tumor after the first is removed via surgery. These biomarkers were initially identified based upon genomic analysis of 36 frozen thymoma samples from patients at the Indiana University Melvin and Bren Simon Cancer Center. Additional tests confirming the results were later performed on 75 other thymoma biopsies provided by other institutions.

“Obtaining objective molecular data to support traditional histological assessment will lead to improved diagnostic accuracy for thymomas and thymic cancers,” said Dr. Badve, professor of pathology and laboratory medicine at IU School of Medicine. “The test is called DecisionDx-Thymoma and provides an objective, accurate assessment of an individual’s risk of metastasis.”

The ability to predict this risk of recurrence — also known as metastasis — will help physicians create individualized treatment plans that avoid side effects caused by adjuvant treatments that may be unnecessary in some patients. Adjuvant treatments, such as radiation and chemotherapy, are given in addition to the primary treatment, such as surgical removal of the tumor.

All development and validation work on the test was performed by Castle Biosciences Inc., a rare cancer molecular diagnostics company whose mission is to serve individuals afflicted with rare or orphan cancers. The test also will be exclusively marketed by the company.

Thymomas are rare but also one of the most common types of cancers found in the upper chest. Tumors are often discovered on a chest X-ray when a patient suffers from chest pain, cough or difficulty swallowing — or a previously associated autoimmune disorder — and can spread throughout the chest and body. Treatment consists of surgical removal followed by radiation or chemotherapy in patients believed to be at high risk for metastasis. Under the traditional disease classification process used to identify the likelihood of metastasis — the Masaoka staging system — a significant number of patients staged as “low risk” still experienced recurrence.

The more accurate assessment of recurrence risk provided by DecisionDx-Thymoma could reduce or eliminate the need for these painful additional treatments after removal in patients who test at a low risk for thymoma recurrence.

“The ability to accurately assess metastatic risk based upon the thymoma’s molecular signature will enable personalizing therapeutic options,” said Dr. Loehrer, director of the IU Simon Cancer Center, H.H. Gregg Professor of Oncology at IU School of Medicine and an international expert on thymomas and thymic carcinomas. “This will assist in deciding which patients should receive postoperative therapy.”

IU is uniquely positioned to collect and analyze thymomas and thymic tumors because of researchers such as Dr. Loehrer, who have been sought by patients for expert care over the past 30 years.

The partnership between Castle Biosciences and the IU investigators was brokered by the Indiana University Research and Technology Corp. in fall 2011 after the group worked with the IU investigators to file disclosure on the genes used in their research before their poster presentation at the American Society of Clinical Oncology in 2011. The partnership with Castle Biosciences provides access to state-of-the-art facilities capable of technical validation of the thymoma test in laboratories accredited by the College of American Pathologists and certified by the Clinical Laboratory Improvement Amendment of the U.S. Food and Drug Administration.

Support for early research was also provided by the Indiana Clinical and Translational Science Institute and IU Simon Cancer Center.

“It is well recognized that rare cancers typically do not have accurate staging systems as it relates to predicting recurrence or metastasis,” said Derek Maetzold, CEO of Castle Biosciences. “We created our company with the focus on working with academic centers such as Indiana University for the purpose of providing objective laboratory reports that would improve staging accuracy and thus improve risk benefit decisions as it relates to individual treatment plans. The DecisionDx-Thymoma test meets this objective.”