Surgery News - September 2007 - (Page 16) ONCOLOGY SURGERY NEWS • S E P T E M B E R 2 0 0 7 Research Improves GIST Prognosis B Y B E T S Y B AT E S Standards Not Met Lymph Nodes • from page 1 Else vier Global Medical Ne ws L A S V E G A S — Although complete resection is the initial treatment of choice for gastrointestinal stromal tumors, advances in their characterization and therapy are providing a more optimistic outlook for patients whose survival was once measured in months rather than years. “These tumors were miscategorized for 20 years,” Dr. Stanley W. Ashley said at a multidisciplinary general session of the spring meeting of the American College of Surgeons. In the late 1990s, Japanese researchers discovered that approximately 75%-80% of gastrointestinal stromal tumors (GISTs) have mutations in the c-kit gene. This advance meant that tumors previously classified as leiomyomas, leiomyosarcomas, and leiomyoblastomas could be correctly recognized as GISTs. Further study revealed that 5%10% of GISTs have a closely related mutation in the PDGFRA gene, while approximately 12%-15% are unrelated to these mutations and therefore characterized as “wild type” or “wild card” GISTs. GISTs, the most common sarcomas of the gastrointestinal tract, account for an official 0.2% of GI malignancies, “but that’s changing” as the incidence increases, said Dr. Ashley, vice-chairman of surgery at Brigham and Women’s Hospital, professor of surgery at Harvard Medical School, Boston, and an ACS Fellow. Autopsy studies suggest that small GISTs exist in much of the population, with triggering genetic mechanisms likely responsible for turning these benign, incidental lesions into the “bad actors” they can become. An important therapeutic turning point was the approval in 2002 of imatinib (Gleevec) for unresectable and/or metastatic GISTs, which drove median survival This CT image shows a bulky abdominal rates for these patients from metastatic gastrointestinal stromal tumor. “at best, 19 months” to about 58 months, said Dr. Martin McCarter, be performed while the tumor is still reassociate professor of surgery at the sponding. Consider selective resection if University of Colorado, Denver, and an focal resistance to the drug is detected. For patients with suspected GISTs ACS Fellow. Adding nuance to basic understand- small enough to be resected, skip the ing, Dr. Christopher Corless, chief of biopsy, suggested Dr. Ashley. The best surgical pathology at Oregon Health tool for preoperative planning is the CT and Science University, Portland, and scan, although endoscopic ultraothers have begun to further charac- sound–guided fine needle aspiration terize mutations according to exons has been used in the upper GI tract. Once macroscopic disease has been within the c-kit and PDGFRA genes. Exon 11 mutations, for example, oc- resected (with negative microscopic cur in GISTs seen throughout the GI margins, if possible), size (greater or tract and are sensitive to Gleevec, as are less than 2 cm for intestinal tumors, and “wild type” tumors. Exon 9 mutations, greater than or less than 5 cm for stomhowever, occur only in tumors arising ach tumors) and mitotic count deterfrom the duodenum, jejunum, ileum, mine prognosis and risk of recurrence. Although tyrosine kinase inhibitors and right colon—“never in the stomach,” Dr. Corless said. They respond to are approved only for advanced disGleevec in standard doses in only about ease, neoadjuvant therapy is recom35%-40% of cases, which suggests to mended by some. “If it’s less than 5 cm, proceed with some the need to increase the dosage surgery,” opined Dr. Ashley, and added given to patients with this mutation. Dr. McCarter recommends that ad- that although Gleevec has greatly imvanced tumors be biopsied, then treat- proved survival for some patients, it is ed with one of the tyrosine kinase in- “no match for the response you get hibitors for 3-6 months. Surgery should with surgery.” ■ Percutaneous Biliary Drainage Does Not Boost Cancer Patients’ Quality of Life BY JANE SALODOF MACNEIL Else vier Global Medical Ne ws C H I C A G O — Percutaneous biliary drainage, a palliative procedure, failed to improve quality of life for cancer patients in a prospective study presented at the annual meeting of the American Society of Clinical Oncology. In a study of 109 evaluable patients, the most common diagnoses were cholangiocarcinoma (30%) and pancreatic cancer (29%), followed by metastatic colorectal cancer (18%) and gallbladder cancer (8%); 15% of patients had other cancers. More than half (58%) of procedures were performed to reduce bilirubin levels. Pruritus (20%) was the next most common indication, followed by cholangitis (12%). The remaining drainages (10%) were prompted by other or multiple complications. The population’s Functional Assessment of Cancer Therapy Hepatobiliary (FACT-Hep) scores declined significantly (P < .0001), which indicated a decline in quality of life during the 4- week study, as did scores on the FACT functional, social, and hepatobiliary subscales. The only observed benefit was a significant improvement in pruritus (P < .0001). Percutaneous biliary drainage “does not improve quality of life, and the goal of palliation is to improve quality of life,” lead author Piera C. Robson, R.N., said in an interview during the poster session. The finding was a surprise to the investigators, who are in the nursing, radiology, and surgery departments at Memorial Sloan-Kettering Cancer Center, New York City. They had achieved technical excellence in doing the procedure, and hoped to demonstrate that draining a bile duct obstructed by cancer would benefit the patients. The investigators approached 230 sequential patients who underwent the procedure from October 2004 to December 2006. Of these, 125 (54%) were eligible and enrolled in the study. The evaluable population comprised 60 men and 49 women with a median age of 66 years (range, 21 to 85 years). All patients completed a questionnaire at baseline, but only 34 did so 4 weeks after their procedures. By that point, 11 patients (10%) had died. At 8 weeks, 30 patients (28%) were deceased, with one death attributed to a procedure-related complication. Median survival was just 4.8 months. Noting the good results in the patients with pruritus, Ms. Robson said, “We found out we should look more at patients getting biliary drainage to find out which subsets do benefit.” In her discussion of the study, Dr. Joanna M. Brell of Case Western Reserve University, Cleveland, praised the investigators for showing that a study can be done in a very sick population. She also agreed that selecting patients who would benefit is important, but said she found the study’s main conclusion difficult to accept. “I think we take it for granted that decreasing serum bilirubin will improve quality of life,” she said, suggesting that the small number of patients who completed the study confounded the results. ■ ing the appropriate time to find the number of lymph nodes in each specimen,” he said in an interview. The second study also found that the proportion of colorectal cancer patients receiving appropriate sampling is unacceptably low, and suggested that staging may suffer as a result, Dr. Qian Cai and her colleagues gathered SEER data from 1990 to 2001 on 221,000 patients aged 18 years or older. Multivariate logistic regression was used to assess the association between staging and sampling 12 or more vs. fewer than 12 lymph nodes. Overall, about 35% of colorectal patients had 12 or more lymph nodes assessed. Among these patients, more than one-third had stage III colorectal cancer. By comparison, less than 20% of patients with fewer than 12 lymph nodes sampled were found to have stage III disease, according to Dr. Cai, a researcher with Abt Associates Inc., in Lexington, Mass. Patients who had 12 or more lymph nodes samWe need to make sure that surgeons pled were 31% more likely to be diagnosed with are doing the stage III rather than stage appropriate II colorectal cancer (P = resections. .001), compared with paDR. RAJPUT tients who had fewer than 12 nodes sampled, Dr. Cai said. Also, patients with the appropriate sampling rate were 41% more likely to have been diagnosed with stage II colorectal cancer than stage I, as compared with the sub-12 node group. Because patients who Greater adherence had 12 or more lymph nodes sampled were sigto guidelines for nificantly more likely to nodal sampling be diagnosed with more should lead to advanced disease, they more accurate may receive more aggresstaging. sive treatment, Dr. Cai DR. CAI suggested. “Greater adherence to the current NCCN recommendations for nodal sampling should lead to improved accuracy in colorectal staging,” she stated with her colleagues. “And improved staging accuracy, in turn, gives clinicians the opportunity to manage treatment more appropriately via adjuvant chemotherapy or other interventions.” Dr. Mitchell C. Posner, discussant on the two poster studies, observed, “Adherence to the guideline for lymph node retrieval greater than or equal to 12 lymph nodes clearly is more likely in NCCN centers, remains an elusive goal for most patients in this country who have resected colorectal cancer, and improves staging accuracy.” “We get it. We agree that 12 lymph nodes is the benchmark that we should use, and I challenge that we should not need to write any more papers about this 12–lymph node target,” added Dr. Posner, an ACS Fellow and the Thomas D. Jones Professor of Surgery and chief of general surgery and surgical oncology at the University of Chicago. Although that goal had not been reached, taken together, the two current studies suggest that progress is being made, he said. ■ COURTESY DR. MARTIN MCCARTER
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