Below is an informal summary of a consensus summary on GIST treatment by an international group of GIST experts. The consensus conference to develop this guideline was sponsored by the European Society of Medical Oncology (ESMO) with a grant from Novartis. A meeting was held in March 2004 among 41 experts from 12 countries from around the world (not just Europe). The resulting paper was published in March 2005 in the Annals of Oncology, volume 16 pages 566-578. The paper is not free-access. This is a paper your oncologist should obtain and read. Its purpose is to continue in the path started by the NCCN guidelines (which it cites) to develop a standard of care for GIST.
The experts came up with 32 points of agreement, with a rating of the degree of agreement and strength of supporting evidence for each point. The points of agreement are integrated into a paper consisting of numbered paragraphs (1 through 14). The following summary maintains the numbered-paragraph structure of the consensus document, but the contents are paraphrased and condensed.
CONSENSUS MEETING FOR THE MANAGEMENT OF GIST
1. Criteria for diagnosis of GIST:
Cell appearance-under-microscope description of GIST subtypes is given.
Immunohistochemical results are as follows…
CD117 or KIT protein: positive in 95% of cases
CD34: positive in 70% of cases
smooth muscle actin: positive in 40% of cases
PS100: positive in 5% of cases
desmin: positive in 2% of cases
2. Mutation analysis:
Molecular analysis for KIT or PDGFRa mutations is a needed clinical step for tumors suspected to be KIT-negative GIST. For other tumors mutation testing is currently a research procedure, but it is expected to be "routine" in the future.
3. Imaging:
CT is the standard imaging technique. MRI is better for imaging rectal GIST. PET is useful when either a) a rapid indication of whether a tumor will respond to imatinib is needed to plan surgery, or b) to evaluate "equivocal images suspected to be metastatic." PET is not mandatory in other cases.
4. Biopsy and Surgery:
There was no consensus regarding the need for a biopsy prior to surgery for a localized resectable tumor thought to be GIST. "If preoperative biopsy is scheduled, because these tumors are very fragile and may bleed easily, an experienced multidisciplinary team is preferred."
Avoid laparocopic surgery for tumors 2 cm or greater.
Surgery techniques and desired margins depend on the location of the tumor (wedge resection is OK for stomach GIST, segmental resection is OK for intestinal GIST, but en bloc resection is often needed for omental or mesenteric disease).
Wide clean margins may not prolong survival but they may prevent metastasis to the peritoneal cavity.
5. Adjuvant treatment with imatinib:
Adjuvant imatinib thereapy means taking the drug after complete resection of localized primary disease (not metastatic disease). Until the results of the current clinical trials of adjuvant imatinib are available, it is an experimental therapy and should not be recommended outside of clinical trials. It was agreed that overall survival, not progression-free survival, should be the appropriate end-point for trials of adjuvant imatinib.
6. Neo-adjuvant imatinib:
Neo-adjuvant use of imatinib means taking the drug prior to surgery. There are no data to support this except when tumor size reduction may affect the feasibility and outcome of surgery, such as to allow function-sparing surgery rather than disabling surgery (especially for anal and esophageal tumors). Neo-adjuvant imatinib should be monitored by a team of GIST experts. This recommendation does NOT apply to patients who need imatinib
to shrink metastatic GIST prior to surgery; imatinib for these patients is
agreed as necessary both before and after the surgery.
7. Follow-up after resection of primary tumor:
There was no consensus regarding monitoring scans after resection. The following suggested scan schedule "was felt to be acceptable" by the group. The document states "At the present time, however, there is no evidence indicating that these are the optimum time intervals, and whether follow-up with CT is beneficial in these patients."
The suggested schedule is as follows:
Low risk tumors (< 5 cm and < 5 mitoses per 50 high-powered fields): CT
every 6 months for 5 years.
Medium or high-risk tumors (5 cm or more, 5+ mitoses per 50 HPF): CT every
3-4 months for 3 years, every 6 months until 5 years, annually after that.
8. Imatinib for advanced GIST:
For unresectable or metastatic GIST there was strong agreement on immediate
treatment with imatinib. When metastatic GIST is completely resectable,
imatinib is still recommended after resection because complete resection of
metastatic GIST is not curative.
9. Optimal dose of imatinib for advanced GIST
400 mg/day is recommended for initial treatment since no overall survival
improvement has been reported in the two large randomized trials comparing
400mg vs 800mg. When longer followup results are available for the ongoing
clinical trials this recommendation may change.
10. Duration of imatinib treatment in advanced GIST:
Imatinib should be continued indefinitely "until progression, intolerance,
or patient refusal." It should not be discontinued.
11. Imaging criteria for tumor response to treatment in advanced GIST:
MRI is an option for imaging liver metastasis. CT is the imaging technique of choice for response evaluation. Qualitative changes in CT appearance of tumors (not size changes) are important because size changes may not occur for a long time, and some tumors may increase in size when responding to treatment. Additional descriptions of qualitative tumor changes are given in the document.
12. Surgical resection of residual metastasis in patients whose residual
disease is controlled by imatinib:
There was no agreement regarding whether to remove residual metastatic disease or stable primary disease that is under control by imatinib. If done, this surgery should be undertaken by an experienced GIST expert team. Imatinib should not be interrupted, or interruption should be only for the shortest possible time.
13. Approaches to progressive disease under imatinib therapy:
Primary resistance is defined as progression within the first 6 months of imatinib treatment. Secondary resistance occurs later than the first 6
months.
Partial resistance includes one or more limited sites of metastasis, or a growing nodule within a larger mass. In the case of partial resistance new trials are needed to determine the utility of metastasis resection or radio frequency ablation.
Multifocal resistance is overt progression of most or all tumor sites. Increasing the dose of imatinib (to 800 mg/day) is recommended in this case.
Alternative options include SU11248 or other drugs given in clinical trials.
14. Strategy for disseminating the consensus document and evaluating its
impact:
Widespread diffusion is desired. There is mention of disseminating the
document on the internet but no specifics are given. Later the panel
intends to evaluate implementation of the guidelines in different countries.
The aim of the guidelines is "to improve the management of GIST patients."