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Researchers Zero In on GI Cancers
Date:1/14/2009

Much effort focuses on genetics and who would benefit from treatments

WEDNESDAY, Jan. 14 (HealthDay News) -- New research may one day help physicians identify those patients with gastrointestinal cancers who are most likely to benefit from certain treatments.

The discoveries, paving the way toward an era of personalized medicine, could save the U.S. health-care system millions while sparing patients the agony of receiving treatments that aren't going to help them.

"These are a diverse group of tumors," said Dr. Jennifer C. Obel, an attending physician at NorthShore University Health System in Illinois, who moderated a Tuesday teleconference on the findings. "More than 270,000 people are diagnosed with GI [gastrointestinal] malignancies in the U.S. every year, and about 135,000 succumb to these illnesses on a yearly basis. How do we distinguish those patients most likely to benefit from treatment and screening than those who are not?"

The findings come from four studies being highlighted at the sixth annual Gastrointestinal Cancers Symposium, in San Francisco.

Gastrointestinal cancers are those that affect the esophagus, stomach, pancreas, liver, small intestines, colon, rectum and anus.

A first study found that testing patients with metastatic colorectal cancer for a specific gene mutation which affects how they respond to therapy, then treating accordingly, could save the U.S. health-care system up to $604 million a year.

The analysis follows on earlier research which found that the monoclonal antibody Erbitux (cetuximab) was only effective in patients who have the normal -- not the mutated -- form of the KRAS gene.

The study authors plugged incidence data on colorectal cancer into an economic model and found that testing for KRAS status in all newly diagnosed patients would cost $13 million, while unnecessarily treating those with mutant KRAS genes would cost $617 million, resulting in a net savings of $604 million.

The study was led by Dr. Veena Shankaran, a postdoctoral fellow at the Veterans Administration Center for the Management of Complex Chronic Care and Northwestern University's Robert H. Lurie Comprehensive Cancer Center in Chicago. It was funded by ImClone Systems Inc., which makes Erbitux.

A second set of researchers reported that people with specific mutations in the epidermal growth factor (EGF) gene and GERD (gastroesophageal reflux disease) have an increased risk of cancer of the esophagus.

Chronic GERD affects some 20 million Americans and is a known risk factor for esophageal cancer, which is on the rise.

A variant of the EGF gene known as G/G was associated with nearly twice the risk of developing esophageal cancer when compared with the A/A "wild type" -- or normal form -- of the gene, but only in individuals with GERD. The apparent danger was magnified when the GERD was more severe, the study found.

Overall, those without significant GERD had a lower risk and those with more GERD had almost 10 times the risk. Those who had GERD more than once a week or who had had GERD for more than 15 years had almost 22 times the risk, the researchers said.

"These findings indicated to us that there was indeed an interaction of some sort between the EGF gene and GERD in the esophagus," said study author Dr. Winson Y. Cheung, a clinical research fellow at the University of Toronto and the Harvard School of Public Health. "This could have important clinical implications for screening."

A third group of researchers, from Germany, found that the drug Sandostatin LAR (octreotide LAR) can slow tumor progression in patients with malignant neuroendocrine tumors of the midgut (the lower part of the small intestines), a rare form of cancer.

Currently, there are few effective therapies for this type of cancer.

"The median time to tumor progression was 14.3 months in the treatment group in contrast to six months in the placebo group," said study author Dr. Rudolf Arnold, a professor of internal medicine at Philipps University in Marburg, Germany. "Octreotide LAR should be considered the standard of care" in this group of patients, he said. Members of the research team have received financial support from Novartis, which makes the drug.

Finally, another team of researchers found that variations in DNA "mismatch repair" genes (those that correct DNA errors) might predict how pancreatic patients respond to different therapies.

Pancreatic cancer is notoriously difficult treat, with five-year survival rates hovering at only 5 percent. But some patients do better than others and the critical question is "why?"

"How to identify those patients remains a clinical challenge," said study author Donghui Li, professor of gastrointestinal medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

"A number of genotypes remain significant predictors of tumor response to therapy, tumor respectability [whether surgery is an option] and overall survival," Li said. One genotype predicted a 94 percent response rate to preoperative chemoradiation, compared to 73 percent in patients without the genotype, the study found.

Median survival for those with a "good" genotype was 25.5 months, vs. 7.4 months for those with a "bad" genotype, according to the researchers.

The symposium is sponsored by the American Gastroenterological Association Institute, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

More information

The U.S. National Cancer Institute has more on GI cancers.



SOURCES: Jan. 13, 2009 teleconference with Jennifer C. Obel, M.D., attending physician, NorthShore University Health System, Illinois; Veena Shankaran, M.D., postdoctoral fellow, Veterans Administration Center for the Management of Complex Chronic Care, and Northwestern University's Robert H. Lurie Comprehensive Cancer Center, Chicago; Winson Y. Cheung, M.D., clinical research fellow, University of Toronto and the Harvard School of Public Health; Rudolf Arnold, M.D., professor of internal medicine, Philipps University, Marburg, Germany; Donghui Li, Ph.D., professor, gastrointestinal medical oncology, University of Texas M.D. Anderson Cancer Center, Houston; study abstracts


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