Professor University of Minnesota Edina, Minnesota, United States
Objective: Desmoid-type fibromatosis (DTF) is a tumor composed of myofibroblast-like cells with variable amounts of collagen deposition. While DTF does not metastasize, it is a poorly circumscribed and locally invasive tumor that often results in significant local morbidity. Sporadic DTF usually bears a mutation in CTNNB1, the gene that encodes beta-catenin. DTF in patients with familial adenomatosis polyposis coli have a mutation in APC. Multiple drugs are used to treat DTF, each with different toxicities and efficacy. Unfortunately, these drugs have not been compared side to side, and the best initial therapy is unknown. Over the years, our institution has come to prefer pegylated-liposomal doxorubicin (PLD) for DTF patients. We aim to determine PLD’s relative efficacy and toxicity profile in patients with progressing DTF who received treatment at our institution.
Methods: We performed a retrospective chart review of patients with DTF who received from 2000 to 2023 and had available clinical information in our electronic medical record (EMR). Demographic data, location of the tumors, symptoms, comorbidities, and clinical benefit data were extracted from the EMR. We used descriptive statistics to present our findings. “Clinical benefit” was defined by the treating physician and reflected an improvement in tumor-related symptoms and/or imaging response.
Results: We reviewed 47 patients, 32 female and 15 male. Twelve patients did not require any therapy upon follow-up, 6 of those had spontaneous tumor regression. The location was abdominal in 15, extremity 12 , thoracic in 8, pelvic in 4, head and neck in 3, paraspinal in 3, multifocal in 1, and unknown in 1. Of the cases where the mutation status was known, CTNNB1 S45F was present in 8 patients, CTNNB1 S45P in 5 patients, and APC in 2 patients. Twenty-two received PLD, which was first-line in 17 patients. In 4 patients, PLD was given after >2 systemic therapies. One patient underwent surgery before treatment with PLD. Of the 22 treated patients, 19 were felt to derive clinical benefit. Two patients had an allergic reaction to PLD and proceeded with different therapy, and only 1 patient progressed on PLD. Eleven patients did not require further therapy after discontinuation of PLD. Of the patients who required further therapy, 1 got ablation and obtained clinical benefit, 5 got sorafenib which was discontinued due to side effects in all cases with clinical benefit reported in 2; 2 were re-treated with PLD obtaining clinical benefit. Therapy was well tolerated in the majority of patients. The most common side effect was hand-foot syndrome, dose reductions or dose delays were required in 18 patients. Two patients had allergic reactions resulting in early discontinuation of treatment. Surprisingly, we noticed that 23/47 patients had a history of psychiatric disease, usually depression/anxiety. In addition, 5/31 women had polycystic ovary syndrome (PCOS); 2 women without PCOS had a mother or sister with PCOS. In addition, 16/47 patients had obesity and 5/47 had hypothyroidism. DTF was associated with pregnancy in 1 patient.
Conclusion: We conclude that PLD is an attractive treatment option for DTF patients requiring treatment. Importantly, responses were observed at well-tolerated PLD doses, often much lower than the initial dose. This indicates that using poorly tolerated PLD doses for DTF is unnecessary. The study has the limitations of its retrospective nature; some patients received treatment from multiple providers at different institutions, which complicated the follow-up. Further studies are needed to determine the best initial treatment, its duration and the best mode of discontinuation. Additionally, the effect of biological factors such as mutation status and the degree of tumor infiltration by normal non-mutant myofibroblasts is unknown. Finally, the striking association of antecedent psychiatric diagnoses, PCOS, and obesity should be further investigated.
