Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

Abstract

Background: Tigilanol tiglate (TT) is a novel small molecule for intratumoral treatment of nonmetastatic mast cell tumors (MCTs) in dogs. In a randomized controlled clinical study, 75% of dogs that received a single TT treatment achieved complete resolution of the MCT by 28 days, with no recurrence in 93% of dogs at 84 days. Critical to TT's efficacy was the area of the wound (tissue deficit) after slough of the necrotic tumor relative to pretreatment tumor volume. Objectives: To analyze data collected during the previous study to (a) describe wounds after slough of treated MCTs and (b) identify determinants of wound area and speed of wound healing. Methods: Wound presence, condition, and area were determined from clinical records of 117 dogs over 84 days after a single intratumoral TT treatment. Results: Tumor slough occurred 3 to 14 days after treatment, exposing granulation tissue in the wound bed. Wound area after tumor slough in general was related to pretreatment tumor volume, with maximal recorded wound area fully evident in 89% of dogs by day 7. In dogs achieving complete tumor resolution, all wounds were left to heal by secondary intention. Bandaging and other wound management interventions only were required in 5 dogs. Time to healing (ie, full re-epithelialization of treatment site) depended on wound area and location on the body, with most wounds being fully healed between 28 and 42 days after treatment. Conclusions: Wound area and healing after slough of TT-treated tumors follow a consistent clinical pattern for most dogs.

Intratumoural Treatment of 18 Cytologically Diagnosed Canine High-Grade Mast Cell Tumours With Tigilanol Tiglate

“…Lameness was an expected adverse event, but two experienced a higher severity during this study. A further patient developed a large tissue deficit (1 of the 2 two largest in the US pivotal study) that healed fully but was 1 of 3 (out of 117 patients) that took longer than 84 days to heal (29,41).…”

“…Tumour volume has been confirmed as a prognostic factor for HGMCT in other studies (14,16). This relationship has not been found with TT treatment across much larger sample sizes when treating low grade MCT (29,41). Owing to the small retrospective cohort size there were too few larger volume HGMCT cases for significant comparison and the post-hoc nature of any statistical analysis regarding efficacy of subgroups would be inaccurate (43).…”

“…The creation of a tissue deficit appropriate to tumour volume is an indicator of efficacy (29,41). In the event of a perceived incomplete tumour response the treatment interval should not be <28 days and any tissue deficit should be allowed to heal before retreatment.…”

Tigilanol Tiglate-Mediated Margins: A Comparison With Surgical Margins in Successful Treatment of Canine Mast Cell Tumours

“…Data used in our analysis are for all dogs that were (a) available for assessment and (b) recurrence free at 12 months after a single TT treatment ( Supplementary Figure 1 ). Further details of the design related to this paper have been published previously ( 9 ).…”

“…In a previous paper we used data from a controlled, randomised clinical trial involving 123 client-owned dogs in the USA to (i) describe wound (tissue deficit) formation following intratumoural treatment of MCTs with TT, (ii) show that the area of individual tissue deficits was primarily related to pre-treatment tumour volume and that body location and cytologically diagnosed grade of the MCTs were unimportant in this respect, and (iii) demonstrate that time to healing (i.e., full re-epithelialisation of the treatment site) was dependent on the area of the tissue deficit and on body location ( 9 ). Here we use a subset of the pivotal study data in relation to the patients that recorded no treatment site recurrence 12 months after the completion of the study.…”