Molecular Therapies Break New Ground in Colorectal Cancer Treatment
Advancements in molecularly targeted therapies have revolutionized therapeutic options for colorectal cancer, according to the presenters of a scientific poster at RSNA 2013.
"In the last decade there have been major changes in the management of colorectal cancer. We've gained a better understanding of the mechanisms driving the disease and developed new molecular therapies," poster co-presenter Rahul A. Sheth, M.D., a radiology resident at Massachusetts General Hospital, Boston, said Sunday. "It's important for radiologists to be aware of the therapies, how molecularly targeted therapies affect tumors, and what oncologists are looking for in image findings."
The increasingly complex, genetically based management of colorectal cancer offers challenges as well as opportunities for physicians, according to Dr. Sheth and co-presenter Arun Krishnaraj, M.D., M.P.H., a radiologist at the University of Virginia, Charlottesville. "As part of the multidisciplinary decision-making team, we need to know the new branch points in the management of colorectal cancer and be able to speak the same language as oncologists," Dr. Sheth said.
Mutational analysis has added a slew of new acronyms to the medical lexicon that convey critical information on colorectal cancer tumors, affecting both prognosis and therapeutic efficacy, the co-authors said.
One example: Mutations in mismatch repair (MMR) genes, due to a heritable genetic syndrome or somatic defects, result in microsatellite instability (MSI). "Tumors with MSI tend to be lower stage and have a better prognosis but may be resistant to conventional chemotherapy approaches," Dr. Sheth said.
Although the angiogenesis inhibitor bevacizumab has not totally delivered on its promise to starve tumors of blood flow, Dr. Sheth said the drug still has a role to play in colorectal cancer. When combined with a first-line chemotherapy drug, it can improve survival rates.
Other therapies produced by mutational analysis help oncologists make treatment decisions for a subset of colorectal cancer patients. Cetuximab is a monoclonal antibody targeted against the epidermal growth factor receptor (EGFR), which is overexpressed in 19 percent of colorectal cancers. However, researchers have discovered that patients will not benefit from anti-EGFR therapy when a mutant form of the oncogene KRAS is also present. KRAS is mutated in up to 40 percent of all colorectal cancers.
Dr. Sheth said new molecularly targeted therapies and drugs have an assortment of unique risks and potential complications that radiologists should also be aware of, including:
- Steatohepatitis, inflammation with concurrent fat accumulation in the liver is a potential toxicity of the drug irinotecan and can obscure liver metastases.
- Thromboemboli may affect patients treated with cetuximab.
- Bowel perforations and pulmonary hemorrhage may occur in patients treated with a combination of bevacizumab and conventional chemotherapy.
The presenters also stressed the important role radiologists continue to play in evaluating the resectability of colorectal liver metastases. "Determining the suitability for surgical resection is a critical branch point in the care of patients with metastatic colorectal cancer," Dr. Sheth said.
View the scientific poster, "Colorectal Cancer in the Era of Molecular Medicine: What the Radiologist Needs to Know," in the Lakeside Learning Center through Friday.
Exhibit and Poster Innovation Survey Continues
While in the Lakeside Learning Center, be sure to participate in a survey to gauge attendee preferences for the presentation format of education exhibits and scientific posters.
William J. Weadock, M.D., of the University of Michigan School of Medicine, is conducting this survey on behalf of the RSNA Radiology Informatics Committee. The survey area is located near the entrance to the Lakeside Learning Center. Attendees will be asked for their feedback about a number of potential innovations to the traditional format, including multimedia enhancements.