A Pilot Study of Intralesional Injection of Triamcinolone Acetonide for Desmoid Tumors
Condition: Fibromatosis
MeSH terms: Fibromatosis, Aggressive; Fibroma
Study type: Interventional
Phase: Phase 1

Summary: 
      There is research supporting treatment of superficial fibromatoses (palmar fibromatosis and
      keloids) with triamcinolone acetonide injections. These lesions are histologically similar to
      deep fibromatoses (desmoid tumors). Currently there is little literature evaluating the
      response of desmoid tumors to injections of triamcinolone acetonide. The investigators aim to
      perform a pilot study evaluating the response of desmoid tumors to intralesional
      triamcinolone. If positive results are observed (based on RECIST criteria), then a phase II
      study will be initiated.
    

Detailed description: 
      Desmoid tumors are proliferations of fibroblasts and myofibroblasts, intermixed with abundant
      dense collagen. Histologically they are similar to superficial fibromatoses such as palmar
      (Dupuytren's disease) and plantar fibromatoses, as well as keloids. Unlike the superficial
      fibromatoses, desmoid tumors are located in the deep tissue and stratified based on an
      abdominal or extra-abdominal location.

      There are currently many treatment options for desmoid tumors. Historically, wide surgical
      resection was the treatment of choice. This often resulted in a disfiguring appearance and
      recurrence was common, with rates between 30 - 40% following resection. Additionally,
      radiation and systemic therapies are performed, with an approximate 26% rate of objective
      response, based on RECIST. These therapies are however not without side effects. Observation
      initially is also a reasonable approach as a recent study reported up to 60% of desmoids
      demonstrating stable disease and 18% spontaneously regressing over a five year period. Longer
      follow-up studies are needed to determine the true natural history of desmoid tumors, but
      there currently is a need for an alternative treatment strategy with increased efficacy and
      fewer side-effects once observation has failed.

      Corticosteroids, such as triamcinolone acetonide, have long been used in the treatment of
      hypertrophic scars and keloids in order to decrease the size of the lesion. Proposed
      mechanisms of action of corticosteroids on keloids and hypertrophic scars include a decrease
      in the production of collagen, dissolution of insoluble collagen (collagenolysis), a decrease
      in the local inflammatory process, and an increased rate of apoptosis of fibroblast and
      inflammatory cells. Recently, reports have evaluated the use of triamcinolone acetonide in
      Dupuytren's disease, a superficial fibromatosis. A randomized controlled trial evaluated
      range of motion in patients following needle aponeurotomy alone and in combination with
      serial triamcinolone injections. They found improved range of motion in the triamcinolone
      cohort up to 24 months following treatment. Similarly, Ketchum et al reported that 97% of
      Dupuytren's nodules showed clinical regression following an average of 3.2 intralesional
      injections with triamcinolone acetonide, although half of these patients did experience
      reactivation of the disease at 1-3 years following treatment.

      Currently there is limited reported experience with treatment of desmoid tumors by steroid
      therapy. Rhee et al reported a case of a chest wall desmoid tumor that recurred after two
      surgical resections and postoperative radiation therapy. They treated the lesion with weekly
      intralesional injections of 120 mg of triamcinolone acetonide for 4 weeks. At six months they
      noted a reduction in the size of the lesion. Similarly, Umemoto et al. reported a case of a
      37 year old male with familial polyposis coli and intra-abdominal desmoid tumors. He was
      treated with oral prednisolone therapy with gradual regression of the lesions. At one year
      and six months following his last operation, the patient had no signs of recurrence of the
      desmoid tumors.

      Based on this background information we aim to perform a pilot study of 10 patients with a
      histologically confirmed diagnosis of extra-abdominal aggressive fibromatosis (desmoid tumor)
      in order to determine the response rate of intralesional injections of triamcinolone
      acetonide. Response will be evaluated using the World Health Organization (WHO) response
      criteria, total volume of the tumor, T2 signal hyperintensity, and RECIST.
    

Intervention name(s): Triamcinolone Acetonide
Intervention type(s): Drug
Intervention description(s): A concentration of 40 mg/ml of Triamcinolone Acetonide will be used for injections with a total dose of 120 mg of Triamcinolone given per injection. The injections will be performed under ultrasound guidance by a fellowship-trained musculoskeletal radiologist. The injection locations will be left to the discretion of the radiologist with the request to attempt to distribute the drug throughout the tumor. A total of three injections will be performed at six week intervals.
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment