Molecular subtypes distinguish low-risk from intermediate and high-risk patients
May 7, 2018, New York — Ralph Weichselbaum, who is today director of the Ludwig Center at Chicago, and Ludwig Board member Samuel Hellman suggested somewhat controversially in 1995 that metastatic cancer could occupy an intermediate state between curable, localized tumors and lethal, systemic disease. They called this state “oligometastasis”—Greek for “a few that spread” —and made the controversial suggestion that many of these patients, depending on the extent of their disease, could be cured with surgery or targeted radiation therapy.
Twenty-three years later, Weichselbaum, Hellman—who is today a Professor Emeritus at the University of Chicago—and colleagues have confirmed their oligometastasis hypothesis with a molecular analysis of tumors from patients treated for colorectal cancer. Published in the current issue of Nature Communications, their paper also identifies molecular patterns that indicate which patients are most likely to benefit from surgery, leading to long-term survival.
“This is a paradigm shift in the treatment of metastatic disease,” said Weichselbaum, who is also the Daniel K. Ludwig Distinguished Service Professor and chair of radiation and cellular oncology at the University of Chicago. “Our results point to a molecular basis for oligometastasis that can pretty reliably predict clinical outcomes. In a series of colorectal cancer patients with limited spread of disease to the liver, we were often able to achieve prolonged survival. We think this approach could be applied to many types of cancer.”
The researchers studied 134 patients (median age 61) with cancer of the colon (72%) or rectum (28%) that had spread to the liver. These patients were treated with perioperative chemotherapy followed by surgical removal of detectable cancer that had spread to the liver.
Extensive molecular analyses sorted patients into three distinct groups, of which the second had the highest 10-year survival rates. The researchers found that this group’s tumors seemed to trigger an immune response that helped curtail new tumor growth. A reclassification of these tumors on the basis of their molecular traits and clinical data predicted a robust difference in survival for the low-risk group: a 94% chance of 10-year overall survival. Groups 1 and 3, meanwhile, had 10-year overall survival of 45% and 19%, respectively.
The researchers say their findings provide a “framework for integrated classification and treatment of metastasis” that should help improve treatment of patients with potentially curable colorectal liver metastases.
A more detailed release from which this summary is derived can be found here.