Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF-03084014) in desmoid tumor: Report of four pediatric/young adult cases

Systemic therapy for pediatric desmoid tumors has been challenged by a lack of high-quality clinical evidence and potential adverse effects. The gamma-secretase inhibitor nirogacestat has shown promising efficacy in adults. We report four cases of pediatric and young adult desmoid tumor patients (three with familial adenomatous polyposis [F.A.P.] syndrome) who received nirogacestat on compassionate use. After a median of 13.5 months (range 6-18), three had durable benefit: a complete response (Case 1); a partial response (Case 2); stable disease (Case 3). The fourth had disease progression after a partial response. No patient experienced grade 3 or 4 adverse events.

Cryoablation (CA) has gained popularity in the treatment of benign and malignant musculoskeletal tumors. While extra-abdominal desmoid (EAD) tumors are not malignant, they remain challenging to treat because of their high local recurrence rate. We reviewed all EAD tumors treated with CA at our institution between November 2012 and March 2020. Fourteen procedures were performed on nine females and one male (mean age, 33 ± 18 years) as either first-line (n = 4) or salvage therapy (n = 6) with curative intent (n = 8) or tumor debulking (n = 2). Treatment outcome was based on the change in enhanced tumor volume (ET-V). For curatively treated patients, the mean ET-V change was -97 ± 7%, -44 ± 143%, and +103 ± 312% at 3, 6, and 12 months, respectively. For debulking patients, the mean ET-V change was -98 ± 4%, +149 ± 364%, and +192 ± 353% at 3, 6, and 12 months, respectively. During a mean follow-up of 53.7 months (range, 12-83 months), one grade III and one grade IV complication were noted.

We retrospectively evaluated the images of 20 patients with histologically proven breast fibromatosis on mammography, magnetic resonance imaging (MRI), and ultrasonography. Altogether, there were 22 lesions: 10 lesions involved the superficial fascia system including four lesions additionally involving the deep fascia and pectoralis major, and 12 lesions were inside the glandular parenchyma with two lesions originated from the prior surgery site. The detection rates of mammography, ultrasound, and MRI for breast fibromatosis were 33.3% (3/9), 90% (18/20), and 100% (3/3), respectively. We found that fascia involvement may be a characteristic of breast fibromatosis. The lesion located inside glandular parenchyma is prone to be underestimated, whereas combined MR with ultrasound is recommended for the diagnosis.

Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents.

A 17-year-old adolescent boy was referred by an orthopaedic physician to physical therapy for chronic left shoulder pain and a clinical diagnosis of labral tear. The physician ordered current radiographs, which were noncontributory. Findings during physical therapy examination warranted referral back to the physician, with a request for magnetic resonance imaging. Magnetic resonance imaging revealed a soft tissue abnormality in the infraclavicular and subcoracoid spaces. The patient was referred to orthopaedic oncology, where biopsy confirmed a desmoid tumor.

We report here the case of a 27yrs old male with aggressive fibromatosis that recurred following a surgical excision, and resulted in hampering the quality of life. The disease was managed using cytotoxic chemotherapy with doxorubicin, resulting in significant clinical and radiological response. It was followed by maintenance regimen using a less aggressive approach with non-steroidal anti-inflammatory drugs such as celecoxib that resulted in further clinical response at 2 months follow up. Therefore, the therapy was further continued.