(24) Hydroxyurea as an Adjuvant Therapy for Treatment of Head and Neck Aggressive Fibromatosis: A Case Report With Long-Term Follow-Up and Review of the Literature

Abstract: Aggressive fibromatosis (AF), or desmoid tumor, is a benign soft tissue tumor of fibroblastic proliferation arising from fascial planes and musculoaponeurotic structures with high potential for local invasion. While AF is relatively rare in the head and neck (~12% incidence), its aggressive nature and high recurrence rate (42% to 62%) pose significant challenges in treatment. Commonly accepted modalities include surgical resection, with or without adjuvant chemotherapy or radiation therapy. However, recurrence rates remain high, prompting exploration of alternative treatments such as hydroxyurea. This study presents a case of pediatric AF in the mandible treated with surgical debulking and adjuvant hydroxyurea, with a 10-year follow-up, alongside a review of relevant literature.

An evidenced-based literature review was conducted; search strategy was devised and PubMed, Google Scholar, and Cochrane electronic databases were searched using the following medical subject headings (MeSH) terms: “aggressive fibromatosis,” “desmoid tumor,” “hydroxyurea,” “adjuvant therapy,” “head and neck.” The references of the articles were also searched for related articles. 

Among 15 identified articles, six discussed hydroxyurea. Among these, none utilized it as primary treatment. Three articles mentioned it as a secondary treatment either after surgery or chemotherapy, and three as tertiary or beyond. Ferrari et al. observed tumor shrinkage in 6 of 16 patients, including three with head and neck (H&N) AF under secondary treatment after primary chemotherapy. Tiwari et al. successfully treated a 6-year-old boy with recurrent AF using hydroxyurea, resulting in 18 disease-free months. Paul et al. reported 16 children with H&N AF, one of which treated with hydroxyurea secondarily, who continued to have disease progression. Zhao et al. reviewed 11 patients, one treated with hydroxyurea as part of multiagent neoadjuvant chemotherapy, and experienced progressive disease. Meazza et al. observed tumor response to oral hydroxyurea in a 15-year-old boy administered after surgery and multiple chemotherapeutics. Takahashi et al. reported a case of deep neck AF refractory to various treatments, including hydroxyurea. Our case involved a 2-year and 9-month-old boy treated with debulking and adjuvant hydroxyurea in 2012, remaining disease-free since 2013 with the last follow-up in June 2023.

Pediatric H&N AF is rare. While the tumor is benign, its aggressive nature and high recurrence rate often makes it difficult to treat. The standard of treatment has been resection with negative margins, however with significant risk for permanent functional and cosmetic impairment. Here, we report a case of AF of the mandible in a 2½-year-old pediatric patient who was treated with surgical debulking with positive margins and adjuvant chemotherapy with hydroxyurea. No recurrence of the tumor has occurred in 10 years, and the patient continues to have normal function, facial and dental growth and healed without cosmetic impairment. A multidisciplinary approach could maximize preservation of anatomical form and function. Further investigation is needed to explore the effects of hydroxyurea on AF and possibly improve patient outcomes, especially in the pediatric population.

References

Balamuth NJ, Wormer RB. Successful treatment of fibromatosis with hydroxyurea: Analysis of 20 pediatric cases. Connective Tissue. London: Oncology Society (CTOS) Annual Meeting; 2008. abs #3485
Tiwari, Charu; Borkar, Nitinkumar. Pediatric recurrent fibromatosis managed by hydroxyurea monotherapy. Journal of Cancer Research and Therapeutics ():10.4103/jcrt.jcrt_51_22, December 15, 2023. | DOI: 10.4103/jcrt.jcrt_51_22