Managing a Recurrence

NOTE: This section of the website applies both to patients with metastatic GIST that have become resistant to Gleevec and for patients that have a recurrence while taking adjuvant Gleevec (preventative Gleevec). It does not apply to patients taking adjuvant Gleevec that stopped taking Gleevec and then had a recurrence at a later date. The latter category of patients should see the Managing recurrence, Initial Recurrence section of the website.

For a more thorough (and more technical) description of managing GIST therapies, including a recurrence, see the guidelines for Soft TIssue Sarcoma published by the National Comprehensive Cancer Network (USA), or other national guidelines as appropriate.

Also see the article, "Managing Progression" by Charles D. Blanke, MD.

1. Make sure that it really is progression.
   • Some tumors that are dying can actually swell and appear larger on a CT scan. This is not progression, but tumors that are responding to treatment. These tumors will usually have a change in density (less dense) and appear darker on a CT scan and the border may become better defined. A PET scan of this type tumor will typically show decreased glucose uptake.
   • Some tumors that have a density very close to the surrounding liver may not show up on an initial CT scan. Treatment with Gleevec can cause these tumors to become less dense and they will then show up on later CT scans. This can be very misleading as they APPEAR LIKE NEW TUMORS!1
   • Not all radiologist will be familiar with these type of responses and may report progression when in fact the tumors are responding to treatment.
2. Consider a consultation with a center that has lots of GIST experience.
   This type of experience can usually be found at some of the larger cancer centers that have a Sarcoma Center. The 2010 NCCN guidelines recommend that "All patients should be managed by a multidisciplinary team with expertise in sarcoma". If you have not previously had this type of support, it's time to consider it.

3. The progression should be categorized as limited progression (example, one or two tumors progressing) or generalized (widespread) progression as they are treated differently. The possibility of a new, second type of cancer must also be considered.
   
   1. Limited Progression 2
   • Continue with the same dose or increase the dose of imatinib as tolerated or change to sunitinib, reassess therapeutic response with a CT scan
   • If resection is feasible, consider resection of progressing lesion(s)
   • Consider radiofrequency ablation (RFA) or embolization or chemoembolization procedure
   • Consider palliative radiation therapy in rare patients with bone metastases. In the NCCN guidelines for treating GIST, this recommendation was based on lower level evidence and there is nonuniform NCCN consensus, but no major disagreement.
   • Also see: Nodule within a mass, a novel pattern of GIST progression
   2. Widespread Progression 2
   • Continue with increased dose of Gleevec (imatinib) as tolerated
     

   OR

   • Change to Sutent (sunitinib); reassess response to therapy with a CT scan.
   • If disease progresses despite treatment with Gleevec and Sutent, strongly consider participation in a clinical trial or consider other off-label options per the NCCN guidelines. The v.1.2010 version of the NCCN practice guidelines for soft tissue sarcoma list 5 drugs that have shown some activity in GIST (although only 2 are approved for GIST by the FDA). These drugs are:
     • Gleevec (imatinib) - Approved as first-line treatment in GIST
     • Sutent (sunitinib) - Approved for GIST patients that have stopped responding to Gleevec or that were unable to tolerate Gleevec.
     • Nexavar (sorafenib)
     • Tasigna (nilotinib)
     • Sprycel (dasatinib)

     NOTE: Off-label treatment may not be covered by some insurance companies and may not be available in many countries.

     CAUTION: In the vast majority of cases, Gleevec or some other type of tyrosine kinase inhibitor should be continued even if the disease is progressing. This is important because stopping the treatment causes the disease to progress faster.

     NOTE: Some patients have had success with reintroduction of Gleevec3 or another previously tolerated and effective tyrosine kinase inhibitor.

   References
1. K. M. Linton, M. B. Taylor, J. A. Radford. Response Evaluation in GIST treated with Imatinib-misdiagnosis of disease progression on CT due to cystic change in liver metastases. 2005 ASCO Abstract 9047
2. Demetri, et al., National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology; Soft Tissue Sarcoma, V.1.2010
3. Fumagalli, E. et al., 2009 CTOS (poster), Rechallenge with Imatinib in GIST patients resistant to second or third line therapy.