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Mutation Status Predicts Probability of Recurrence

January 30, 2011


http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=103&abstractID=70633

JULIE:

The link above gets you the abstract below, presented ealier this month at the ASCO GI Cancer Symposium. As you may recall, several papers have indicated that patients with a KIT mutation affecting one certain part of the KIT protein (the part coded by codons 557 or 558) might have a worse prognosis, a greater chance of metastasis. This study looked at that.

"A" groups had mutations affecting neither 557 nor 558 (A1) or mutations affecting only one of the pair 557 or 558 (A2).


"B" groups are harder to understand from the abstract:

B1 = "only 557-558" B2 = "both 557 and 558" (and some more codons, perhaps?? This is where I cannot figure out exactly what they mean)

Anyhow, the percentage of people having no recurrence was higher for As than for Bs.

The statistical analysis gave a significant difference only for the difference between the A groups and the B2 group, but the raw data show both B groups to be similar, with 50-60% recurrences.

Bottom line: this is a factor to consider in patient decisions about adjuvant imatinib. A high-risk tumor affecting both codons 557-558 is predicted to be especially likely to metastasize. On the other hand, high-risk status did NOT significantly predict recurrence in this study if the mutation did not affect codons 557-558.


Impact of c-kit mutations, including codons 557 and/or 558, on the recurrence-free survival after curative surgery in patients with GIST. J Clin Oncol 29: 2011 (suppl 4; abstr 12) Author(s): T. Watanabe, H. Cho, T. Yoshikawa, A. Tsuburaya, O. Kobayashi; Kanagawa Cancer Center, Yokohama, Japan

Abstract:

Background: Recently, c-kit exon 11 deletions, including codons 557 and/or 558, have been reported to predict a worse prognosis in GIST patients. However, it is difficult to prove the correlation between genotype and tumor aggressiveness in the imatinib- adjuvant era because exon 11 mutations respond well to imatinib. In this study, we evaluated the impact of c-kit mutational status on recurrence-free survival (RFS) after resection of primary GIST.

Methods: Clinical and pathological characteristics of 89 GIST patients in our single institution study were retrospectively analyzed. Tumors were categorized into 4 subgroups based on their mutational locations; A1: mutated codons including neither 557 nor 558, A2: either 557 or 558, B1: only 557 and 558, B2: both 557 and 558. All of the patients underwent curative surgery, and none received adjuvant imatinib. The median duration of follow-up was 49 months.

Results: Tumors originated from the stomach (n=75/89, 84%), small intestine (n=10), and colorectum (n=4). Mutation subgroup B was associated with both Fletcher and Miettinen high-risk categories. The 2-year recurrence free survival rate for A1, A2, B1, B2, was 84.9%, 85.7%, 50%, 57%, respectively. Group B2 had a significantly worse RFS than groups A1 (p=0.0004) and A2 (p=0.0014). Multivariate analysis for RFS indicated that only the mutational subgroup was a significant prognostic factor (p=0.03, HR=2.42).

Conclusions: C-kit mutations, including both 557 and 558, affected the RFS of GIST patients after curative surgery, but those including either 557 or 558 did not. Our results indicate that the locations of c-kit mutations are associated with PFS, and they may therefore affect the selection of candidates with GIST for adjuvant imatinib.