Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

Abstract

Background: Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone.

Results: Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone.

Conclusion and clinical importance: This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs.

Figure 1

Survival curves of dogs with histologic grade 2 and 3 MCTs. Kaplan-Meier survival curves comparing disease-free interval (A) and overall survival times (B) of dogs with histologic grade 2 and 3 MCTs.

Figure 2

Survival curves of dogs with and without c-KIT mutations. Kaplan-Meier survival curves comparing disease-free interval (A) and overall survival times (B) of dogs with and without c-KIT mutations.

Figure 3

Survival curves of dogs with different KIT staining patterns. Kaplan-Meier survival curves comparing disease-free interval (A) and overall survival times (B) of dogs with MCTs with different KIT staining patterns.

Figure 4

Survival curves of dogs with grade 3 MCTs treated with surgery alone or with post-operative chemotherapy. Kaplan-Meier survival curves comparing disease-free interval (A) and overall survival times (B) of dogs with histologic grade 3 MCT treated with surgery alone or with vinblastine and prednisone in addition to surgery.

Figure 5

Survival curves of dogs with c-KIT mutations treated with surgery alone or with post-operative chemotherapy. Kaplan-Meier survival curves comparing disease-free intervals (A) and overall survival times (B) of dogs with c-KIT mutations treated with surgery alone or with vinblastine and prednisone in addition to surgery.