The National Comprehensive Cancer Network (NCCN) GIST task force, including GIST experts in oncology, surgery, pathology and research from around the world, met in December of 2006. In July, The Journal of the National Comprehensive Cancer Network published the updated treatment recommendations of the task force.
The report, “NCCN Task Force Report: Management of Patients with Gastrointestinal Stromal Tumor (GIST) – Update of the NCCN Clinical Practice Guidelines”, is available on the NCCN website (www.nccn.org). Physicians and medical professionals can apply for continuing medical education (CME) credits upon completion of the course. Dr. Margaret von Mehren, director of sarcoma oncology at Fox Chase Cancer Center, also gave an online presentation covering this topic on the Medscape website (also approved for CME).
The task force took the strongest stance to date supporting the use of genotyping in GIST. The task force “. . . strongly encourages that mutational analysis be performed if imatinib therapy is begun for unresectable or metastatic disease.” They also noted, “Mutational analysis can be considered for patients with primary disease, particularly those with high-risk tumors.” Mutational testing can be done from any available paraffinembedded tumor sample: primary, recurrent, or metastatic.
A new risk assessment table was included in the report. This table was adapted from work done by Dr. Marku Miettinen and Dr. Jersey Lasota at the Armed Forces Institute of Pathology (AFIP). The data in this table was developed based on long-term follow-up of 1055 gastric, 629 small intestinal, 144 duodenal and 111 rectal GISTs. The updated table adds primary tumor location to the existing parameters of primary tumor size and mitotic index to assess the risk of a recurrence after the removal of a primary tumor.
The report includes recommendations for the management of side effects caused by both Gleevec and Sutent. Also included are tables listing potential drug interactions for both Gleevec and Sutent. For the first time, a specific recommendation was made to limit Tylenol (acetaminophen) for patients taking Gleevec. The report noted that “For most patients, this means taking 1300 mg acetaminophen per day or less”.
A detailed discussion of the principles of surgery for GIST and need for multidisciplinary management was presented. Noteworthy in this discussion were:
Recommendation for all GISTs two cm in size or greater to be resected.
The expanding role for laparoscopy was noted. Two studies that demonstrated a low recurrence rate were cited. The report noted that “Generally, gastric GISTs five cm in size or less may be removed by a laparoscopic wedge resection.
The indications for surgery in recurrent or metastatic GIST.
Surgery is now recommended in addition to tyrosine kinase inhibitors for selected patients with metastatic GIST
A discussion of “subclinical GISTs”. In a study that examined whole stomachs removed from 100 gastric cancer patients (not GIST patients), 35 patients had very small GISTs (less than 5mm in size) in their stomach. Apparently many people have very small “GISTs” that never develop enough to become noticeable.
Multidisciplinary management of GIST was emphasized.
“Thus, patients with GIST need to be managed with combined pathology, medical oncology, surgical oncology, and imaging expertise in both initial evaluation and management as well as in continued followup. Reducing recurrent disease, optimizing timing of surgery and organ preservation, prolonging survival, increasing the number of resectable cases by pharmacologic debulking, and possibly enhancing response to imatinib by surgical cytoreduction are all potential benefits of multidisciplinary management.”
The report also noted that “In general, patients should be managed by a multidisciplinary team with expertise in sarcoma or tumors of the GI tract”. In addition, they noted, “Any GIST patient with complicated or unusual features or those patients with advanced refractory disease should be appropriately referred to a center with specialty expertise and experience in the management of GIST.”
An excellent discussion on imaging was also presented in the report. Included was a discussion of the “Choi” criteria for CT scans and when and how to use PET scans.
One caveat that should be mentioned is that the task force met prior to two potentially important studies that were presented at the annual American Society of Clinical Oncology (ASCO) meeting in June. These were the report of the meta-GIST analysis. In this study, data from the two large phase III trials were combined. Of particular note in this study is that the combined data on exon 9 tumors showed a statistically significant progression-free survival (PFS) time for high-dose Gleevec whereas the data from the U.S./Canadian trial did not. The other study of particular interest at ASCO was the report by Dr. Ronald DeMatteo that showed that adjuvant Gleevec significantly increases recurrence- free survival time.