This is a follow-up to an article published in the May 2008 newsletter highlighting the benefits and risks involved in MRIs, PET and CT scans.

In the offices of the Life Raft Group, we receive reports of many CT scans findings that are inconclusive. On a regular basis, scans results are misinterpreted as resistance leading to the premature cessation of imatinib therapy which has the potential to reduce long-term survival. This is of greater concern when the radiologist reading the scans has little experience with GIST or when a patient is not consulting with a GIST specialist. Traditional criteria for the evaluation of tumor resistance are likely to overdiagnose the occurrence of progression. Proper use and interpretation of CT scans is vital for effective GIST treatment. Some experts in GIST imaging are now advocating the routine use of both CT and PET scans for GIST. At the present time however, CT (or MRI) is the recommended imaging method according to the NCCN sarcoma practice guidelines (v.1.2008). The guidelines also state to “Consider PET” and that “PET is not a substitute for a CT.”

Initial Response to Therapy

Frequently, the initial responses of GIST to imatinib therapy do not meet Response Evaluation Criteria in Solid Tumor (RECIST) guidelines for treatment response. GIST tumors may decrease in size slowly or only show a cessation of growth while responding well to treatment. In some cases, tumor size may increase due to hemorrhaging within the tumor, necrosis (tumor cell death) or tumor degeneration. How, then, can treatment success be evaluated?

PET Scans: When available, positron emission tomography (PET), using fluorine- 18-fluorodeoxyglucose (18FDG) is an excellent tool for evaluating response. Unfortunately due to cost and machine availability PET scans are not available to all patients. Alternatives for PET scans will be discussed later in this article.
If a doctor considers using PET to monitor therapy with Gleevec, Sutent or another tyrosine kinase inhibitor, a baseline PET scan should be obtained before the start of treatment. This provides a tool for comparison of future scans, allowing for evaluation of response.

Using PET scans, it is possible to observe responses to imatinib therapy in as little as 24 hours after initiation of treatment. Significant decreases in activity on PET scans can be seen within a month of starting imatinib therapy in patients that are responding to treatment. However, it may take appreciably longer for tumor shrinkage to appear on CT scans even when there is a strong benefit from treatment.

Those patients with primary resistance to imatinib therapy may also be identified using PET scans. These patients may show little to no decrease in activity on a PET scan. At this point it may be advantageous to consider alternatives to imatinib.

CT Scans: Although significant changes in tumor size may not be seen using computed tomography (CT), other changes in tumor characteristics make CT scans valuable in the evaluation of initial response. Tumor density changes may be visible in a single month following the initiation of imatinib therapy in responding tumors. Changes in density have been seen in as little as a single week. In addition to a decrease in tumor density, a decrease in vascularization may be seen. These changes have been shown to strongly correlate to activity reduction on PET scans. In contrast, using size alone may not show positive tumor response. In patients with primary resistance to imatinib therapy, changes in tumor density and vascularization may not appear indicating a need to explore alternative therapies.

GIST liver metastases that are responding to treatment may become more cystic during imatinib treatment and therefore more visible on a CT scan. Some lesions may not be visible on a CT scan prior to initiation of imatinib therapy and appear as they respond to treatment. Care must be taken not to misinterpret these findings as progression and prematurely cease imatinib therapy.

Long-term surveillance of tumor response

Both CT scans and PET scans have roles to play in the long-term surveillance of GIST response to imatinib. Traditional RECIST criteria diagnose recurrence or progression based on an increase in tumor size or the identification of new lesions, either at the same site as the primary (a local recurrence) or at distant sites (metastases). Although an increase in tumor size is still important for identifying progression in GIST, the appearance of the tumor needs to be evaluated as well.

CT scans:

As mentioned earlier, it is important to evaluate the density and vascularization of a GIST tumor when evaluating progression. Changes in size without changes in these other tumor characteristics may not indicate progression. In addition, it is possible for a GIST tumor to develop intratumoral (within the tumor) nodules when secondary resistance first begins developing. An intratumoral nodule will appear as change in density and structure.

PET scans:

PET scans are very useful for identifying the onset of secondary resistance. When the results of a CT scan are inconclusive or inconsistent with clinical observations, a PET scan may help clarify the situation. When secondary resistance develops, an increase in activity is seen on a PET scan. The use of PET scans may help with early identification of progression as well as prevent misdiagnoses of progression.

Both PET and CT scans are valuable tools in the evaluation and surveillance of GIST. Traditional RECIST criteria may over-diagnose primary resistance and progression. When available, PET scans are an excellent tool for clarifying questionable scans. However, when PET scans are not feasible, evaluation of additional tumor characteristics such as density may help reduce the misdiagnosis of resistance.

Benjamin RS, Choi H, Macapinlac HA et al. We should desist using RECIST, at least in GIST. J Clin Oncol 2007;25:1760–1764 Choi, Haesun Response Evaluation of Gastrointestinal Stromal Tumors Oncologist 2008 13: 4-7; doi:10.1634/ theoncologist.13-S2-4 Demetri GD, von Mehren M, Blanke CD et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347:472–480. Van den Abbeele, Annick D. The Lessons of GIST–PET and PET/CT: A New Paradigm for Imaging Oncologist 2008 13: 8-13; doi:10.1634/ theoncologist.13-S2-8 NCCN Sarcoma Practice Guidelines in Oncology – v.1.2008 Demetri, Benjamin, Blanke, et al., NCCN Task Force Report: Optimal Management of Patients with Gastrointestinal Stromal Tumor (GIST Update of the NCCN Clinical Practice Guidelines Journal of the National Comprehensive Cancer Network, Volume 5, Supplement 2