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

Reddell, Paul; Ridder, Thomas R De; Morton, John M.; Jones, Pamela D; Campbell, Justine; Brown, Graham; Johannes, Chad M.; Schmidt, Péter; Gordon, Victoria

doi:10.1111/jvim.16009

Cited by 14 publications

(31 citation statements)

References 16 publications

(49 reference statements)

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“…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).…”

Section: Resultsmentioning

confidence: 99%

“…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).…”

Section: Discussionmentioning

confidence: 97%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Brown¹,

Campbell²,

Jones³

et al. 2021

Front. Vet. Sci.

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Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

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

Brown¹,

Campbell²,

Jones³

et al. 2021

Front. Vet. Sci.

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“…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 ).…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Ridder¹,

Reddell²,

Jones³

et al. 2021

Front. Vet. Sci.

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Tigilanol tiglate (TT) is a novel small molecule registered as a veterinary pharmaceutical for intratumoural treatment of canine mast cell tumours (MCTs). The drug has a multifactorial mode of action resulting in rapid destruction of the treated tumour by haemorrhagic necrosis and subsequent slough of the necrotic tumour to reveal a tissue deficit that is left to heal by second intention with minimal to no veterinary intervention. Here we introduce the concept of TT-mediated margins, the calculated margin of tissue loss analogous to surgically applied margins to help clinicians conceptualise tissue deficits formed following tumour destruction by TT relative to surgical excision. We used data from 51 dogs that were recurrence-free 12 months after a single administered TT dose into a single target MCT <10 cm3 in volume in a randomised, controlled clinical trial in the USA. We calculated TT-mediated margins based on length of the longest axis of (i) the tumour prior to treatment and (ii) the maximum tissue deficit formed 7–14 days after TT treatment. We compared these TT-mediated margins for each tumour to two surgical approaches to MCT excision in general practise: modified proportional margins (with 2 cm upper limit) and 3 cm fixed margins. For most dogs, TT-mediated margins were less than half the length of the margins calculated for the two surgical approaches in removing the same tumour. There was a trend for TT-mediated margins to increase with increasing tumour volume. Nonetheless, even for the larger tumours in this study (>2 cm3 volume), 50% of TT-mediated margins were less than half the length of the two surgical margins. Eighteen cases were lower limb MCTs, sites often surgically challenging in veterinary practise. On these lower limbs, TT-mediated margins were less than half the length of the corresponding proportional margins in 56% of cases and larger than proportional margins in only two cases. This study suggests that, in many cases, smaller and more targeted margins could be expected when treating MCTs <10 cm3 volume with TT compared with surgical excision. TT-mediated margins are a novel approach to conceptualise tissue deficits after intratumoural TT treatment.

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Clinical evaluation of neoadjuvant tyrosine kinase inhibitor administration for mast cell tumours in eight dogs

Kanai

Sato

Yamauchi

et al. 2023

Vet Record Case Reports

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Complete surgical removal of tumour cells is the first‐line treatment for canine cutaneous mast cell tumours. Surgical removal of mast cell tumours sometimes requires radical surgery. This may cause severe complications, loss of biological function or poor cosmetic outcomes. This report describes the clinical outcomes of preoperative administration of an effective tyrosine kinase inhibitor for mast cell tumours. Five of eight cases responded to tyrosine kinase inhibitors; complete removal was possible in three cases with narrower (<1 cm) surgical margins than the conventional tumour margin estimated from the original tumour size. Mast cell tumours may not require wide resection if they are responsive to tyrosine kinase inhibitors before surgical removal. Preoperative administration of tyrosine kinase inhibitors could be a treatment option for dogs that have difficulty with complete removal causing severe surgical complications, or for owners who do not accept loss of biological function or poor cosmetic outcomes.

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

Cited by 14 publications

References 16 publications

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

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

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

Clinical evaluation of neoadjuvant tyrosine kinase inhibitor administration for mast cell tumours in eight dogs

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