Thursday, January 22, 2009
The 2009 Gastrointestinal Cancers Symposium -- co-sponsored by the American Gastroenterological Association Institute, American Society of Clinical Oncology (ASCO), American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology -- took place Jan. 15 to 17 in San Francisco and attracted about 3,000 attendees from around the world, including 2,750 professionals. The symposium featured more than 500 abstracts on gastrointestinal cancers including cancers of the esophagus, stomach, hepatobiliary, pancreas, small bowel, colon and rectum.
"The major theme coming out of this cancer symposium is that we're going to be able to use biomarkers within patients' tumors to predict prognosis as well as benefit from chemotherapy," said Jennifer Obel, M.D., of the North Shore University Health System in Evanston, Ill., chair of the symposium news planning team. "We're realizing that cancer is a multi-step process with multiple abnormalities and proteins and genes within the tumor. So if we can identify them and find drugs that are tailored to them -- which we've done at record rate in this meeting -- we're going to be improving our care."
As examples, Obel cited two studies that promise to improve care in patients with pancreatic cancer. "Pancreas cancer poses the most significant challenge for all of us treating GI malignancies," Obel said. "In patients who undergo resection for cure of pancreas cancer, only 5 percent are still alive after five years. If we give adjuvant chemotherapy, five-year survival still only approaches 20 percent. So a majority of patients actually have micro-metastatic disease when they're diagnosed with what is perceived to be early-stage pancreas cancer. We want to predict who is at greatest risk of recurrence so we can use therapies wisely."
In one study, Andrew V. Biankin, Ph.D., of the Garvan Institute of Medical Research in Darlinghurst, Australia, and colleagues evaluated 17 biomarkers in 601 patients who underwent pancreatectomy. They found that only one biomarker -- the S100A2 calcium-binding protein -- was an independent predictor of survival. They found that patients with S100A2-negative tumors had a significant median survival advantage compared to those with high-expressing tumors (19.4 months versus 8.8 months) even in the presence of involved surgical margins or lymph node metastases (15.7 months and 17.4 months, respectively).
"S100A2 expression is the best predictor of response to pancreatectomy for pancreatic cancer reported to date, and high S100A2 expression may represent the development of a metastatic phenotype," Biankin and colleagues conclude. "Prospective measurement of S100A2 expression in diagnostic biopsies has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target loco-regional disease."
In a second study, Donghui Li, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues conducted a DNA analysis on blood samples from 154 patients who were already participating in a clinical trial to test the benefit of radiation therapy and chemotherapy in combination with gemcitabine and were possible candidates for surgery. They found that malfunctioning mismatch repair genes were significantly associated with patient response to chemoradiation and overall survival. Three to five years after diagnosis, they found that 20 of 25 patients with zero or one adverse genotype were still alive while those with two, three, four, five or six-seven adverse genotypes had median survival times of 36.2, 23.9, 16.3, 13 and 8.3 months, respectively.
The researchers concluded that analysis of mismatch repair genes is a potential predictor of response to gemcitabine-based therapy and a possible prognostic marker for tumor respectability and overall survival.
"Some patients who are treated for pancreatic cancer do better than others, and these findings help us to understand why this is the case," Li said in a statement. "As we dig deeper into genetics and personalized medicine, we are gaining new insights into the genetic differences between patients who are successfully treated and those who are not. Such findings will eventually help us to select the best treatment for each patient."
"Another study showed that pancreas cancer patients with a genetic variant of a certain metabolic enzyme were at significant risk of toxicity from gemcitabine," Obel said. "So the dosing of our chemotherapy as well as the risk of recurrence will be impacted by this kind of research."
In that study, James Farrell, M.D., of the University of California Los Angeles, and colleagues conducted a DNA analysis of 98 pancreatectomy patients who received radiotherapy with 5-FU and 87 pancreatectomy patients who received radiotherapy with gemcitabine. They found that a cytidine deaminase single nucleotide polymorphism -- (79A>C (Lys27Gln)) -- was a predictive marker of gemcitabine hematologic toxicity but not of disease-free survival or overall survival at 18 months.
Obel predicted that genotyping of patients with GI cancer could become standard practice within five years. "Within two years of the publication of studies showing that patients with KRAS-mutated metastatic colorectal cancer derived no benefit from EGFR inhibitors, KRAS testing moved into the clinic. Now, as a practicing oncologist, I do not treat patients with metastatic colorectal cancer until I know their KRAS status. So we're all encouraged by the new data on biomarker development. At ASCO, we've dedicated the next year to the advancement of personalized medicine. Although we still need to validate these biomarkers, our cooperative group studies are all designed to validate them."
GCS: Genetic Testing Would Avoid Unnecessary Treatments
FRIDAY, Jan. 16 (HealthDay News) -- Universal KRAS testing of metastatic colorectal cancer patients to identify tumors that do not respond to cetuximab could save more than $600 million a year in unnecessary treatment costs, according to research presented at the sixth annual Gastrointestinal Cancers Symposium held Jan. 15 to 17 in San Francisco.
GCS: Reflux Disease and Gene Linked to Esophageal Cancer
THURSDAY, Jan. 15 (HealthDay News) -- In patients with gastroesophageal reflux disease, certain mutations in the epidermal growth factor gene are associated with a significantly increased risk of esophageal cancer, according to research presented at the sixth annual Gastrointestinal Cancers Symposium held Jan. 15 to 17 in San Francisco.
GCS: Drug Shows Promise in Treating Rare, Midgut Cancer
THURSDAY, Jan. 15 (HealthDay News) -- In patients with rare malignant neuroendocrine tumors of the midgut, treatment with octreotide LAR -- a drug approved in the United States to treat certain pituitary gland disorders and to reduce diarrhea caused by other types of benign gastrointestinal tumors -- may significantly slow tumor progression, according to research presented at the sixth annual Gastrointestinal Cancers Symposium held Jan. 15 to 17 in San Francisco.
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