NCCN Gastrointestinal Stromal Tumor Updates

This year's updates parse sarcomas, emphasize the importance of accurate pathology evaluations, and examine the value of molecular testing.

At the National Comprehensive Cancer Network (NCCN) 15th Annual Meeting, George D. Demetri, MD, The Dana Faber Cancer Institute, presented updates to the NCCN Gastrointestinal Stromal Tumor (GIST) Guidelines. This year’s updates parse sarcomas, emphasize the importance of accurate pathology evaluations, and examine the value of molecular testing, which is increasingly finding a role in assessing solid tumors such as GIST.

Demetri started the session by noting that GISTs were historically thought to be “big bad cancers,” but that gastroenterologists have pointed out that these cancers are often observed when they are tiny and surgical resection is curative. “Lesions less than 2 cm are, in fact, probably a different bird from the big, bad, life-threatening GIST that most of us in our oncology department are likely to be seeing,” said Demetri. While no gastroenterologists were included on the NCCN GIST Panel, Demetri noted that future versions of the guidelines will likely include gastroenterology input.

Another important predictor of risk comes from pathology evaluations, an area where NCCN pathologists from institutions such as Dana Farber, Memorial Sloan-Kettering Cancer Center (MSKCC), and MD Anderson have expertise, noted Demetri. These pathologists have discovered the importance of actually counting the number of mitoses per 50 per high powered fields, rather than estimating. "We see a lot that are diagnosed with 5. The NCCN pathologists indicate you really need to count 50 because there's variation, and low mitoses may mean lower risk,” he noted. The NCCN revisions also outline the value of molecular testing. For instance, “KIT and PDGFRA have important ramifications for prognosis as well as possibly for therapy,” said Demetri.

The workup of patients presenting with GIST should include endoscopic ultrasound (EUS), “which can be a very useful tool for the baseline evaluation of these patients,” said Demetri. GISTs with high-risk EUS features require complete surgical resection, whereas those with no high-risk EUS features may require only endoscopic surveillance. This is an area where future guidelines will likely incorporate input from gastroenterologists, noted Demetri.

The guidelines this year also deemphasize PET scanning. Although Demetri said it is a good tool, many NCCN panelists felt that the emphasis was too heavy previously, as much of the information obtained through a PET scan can be gotten from a CT scan. Worldwide, imatinib (Gleevec) is considered the gold standard as a first-line therapy in patients who truly have GIST. An assessment of therapeutic affect within 3 months of initiating therapy can be done with CT alone, noted Demetri. "We've really tried to dampen down what was taken from prior guidelines: that everyone with GIST needs a PET scan, as that's not what we were trying to say," he said.

Adjuvant Imatinib

According to Demetri, not all patients need to receive imatinib in the adjuvant setting. “We foresaw there were patients who were completely resected—a clean population—the important thing in the guidelines is that those patients should be considered for imatinib in the adjuvant setting only if there is significant risk of recurrence,” he said. Patients with large GISTs with no mitotic activity have a reasonably low to intermediate risk and may not need adjuvant imatinib, he noted. When it comes to duration of imatinib in the adjuvant setting, it is generally given for 12 months, but the optimal duration is still unclear, and research has shown that once imatinib stops, risk comes back. Currently, there are some large scale trials looking at longer durations of adjuvant therapy. “We don't give 1 year of tamoxifen. Why are we giving only 1 year of adjuvant imatinib?” questioned Demetri.

Future of NCCN GIST Guidelines

A major ongoing project to continually improve NCCN guidelines for soft tissue sarcomas includes developing comprehensive lists of possible chemotherapeutic and other treatment options for sarcoma patients using agents approved by the FDA for some indication, even if that indication is not sarcoma. This is important because the only chemotherapy approved for sarcoma is adriamycin, which has been available for 40 years, and treatments are limited. “We are going to use a metric of public literature, presentations, something vetted by someone else as a paradigm for trying to come up with a listing of drugs with activity in soft tissue sarcoma,” said Demetri. “One might say that's a pretty low bar to jump over, but we need a different standard of evidence because we won’t be able to get large cohorts of patients together as in breast cancer, for example.” One of the agents added to the current list for PEComa, an exceptionally rare sarcoma, is a simple agent sirolimus. This agent was added because collaborations between Demetri and colleagues at Dana Faber and experts at MSKCC found that this agent showed some activity in these sarcomas. Demetri cautioned, however, that when clinicians refer to the drug listings in the guidelines that they understand that they do not reflect a hierarchy. “It's really kind of a random list,” he noted.