Deni Study: Real-World Data on the Use of Nirogacestat in Patients With Desmoid Tumors in the French Sarcoma Group

The DeFi trial revealed a significant improvement in progression-free survival (PFS) with nirogacestat in patients with desmoid tumors. The DeNi study reports outcomes of patients treated with nirogacestat through the French compassionate use program. DeNi is a retrospective, real-world study. Outcomes included objective response, pain improvement, 1-year PFS, and toxicity. Between February and June 2024, 55 patients with desmoid tumors were included (37 women). Data were updated until November 2025. The median age was 38.6 years (range: 18.0-66.7). The median number of previous therapies was 2, including local therapies. The median follow-up was 21.4 months [95% CI: 19.5; 25.6]. The estimated median duration of nirogacestat treatment was 16 months. Partial response and stable disease were observed in 33 (60%) and 17 patients (31%), respectively. The 1-year PFS rate was 76.2%, and 77.0% of patients remained without treatment change at 1 year, including patients with dose reductions. Of the 49 patients with baseline pain, 38 (78%) experienced pain improvement under nirogacestat; 35 (71%) reduced or discontinued analgesics. The most frequent side effects (all grades) were diarrhea (53%), fatigue (47%), and rash (29%). Thirteen patients (24%) required dose reduction: 11 for digestive adverse events (85%), 1 for mucositis, and 1 for fatigue with hypertension. The DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase III DeFi trial.

Introduction: Intra-abdominal desmoid tumors (DTs) are rare non-metastatic fibroblastic neoplasms that commonly develop at sites of prior surgical trauma or inflammation. Here, we report a diagnostically challenging case of a DT mimicking tumor recurrence or primary malignancy following laparoscopic distal pancreatectomy.

Case presentation: A 69-year-old woman with a history of laparoscopic ileocecal resection for Stage I cecal cancer underwent laparoscopic distal pancreatectomy with splenectomy for suspected pancreatic cancer. Histopathology of the resected pancreas revealed low-grade pancreatic intraepithelial neoplasia (PanIN-1/2), which was considered responsible for the main pancreatic duct obstruction, with a minute neuroendocrine tumor (NET) (Grade 1, 1.9 mm) identified in the vicinity. The patient developed a Grade B postoperative pancreatic fistula (POPF) requiring prolonged drainage. Ten months later, follow-up CT revealed an 18-mm nodule in the transverse mesocolon. 18F-fluorodeoxyglucose PET/CT (FDG-PET/CT) demonstrated intense focal FDG accumulation (maximum standardized uptake value = 4.6), whereas somatostatin receptor scintigraphy was negative. The tumor grew rapidly to 31 mm over 4 months. Differential diagnoses included recurrence of the primary NET, peritoneal dissemination from occult pancreatic adenocarcinoma (given the PanIN background), or a primary mesenteric gastrointestinal stromal tumor. Due to a high suspicion of malignancy, laparoscopic diagnostic resection was performed. Intraoperatively, the tumor was found to have infiltrated the mesentery of the transverse colon and jejunum, requiring delicate dissection to preserve the middle colic artery and first jejunal vessels. Histopathological examination revealed a spindle cell neoplasm with nuclear accumulation of β-catenin, ruling out malignant recurrence and confirming a DT. Chronic chemical irritation resulting from the preceding POPF is considered a likely trigger.

Conclusions: Intra-abdominal DTs can mimic malignant recurrence on FDG-PET/CT after pancreatic surgery. This case highlights that clinicians should include DTs in the differential diagnosis of mesenteric masses arising at the site of prior postoperative complications, such as a pancreatic fistula.

Background/Objectives: Breast fibromatosis (desmoid-type fibromatosis) is a rare, locally aggressive neoplasm that may closely mimic breast carcinoma on imaging. Occurrence in male patients is exceptionally uncommon, particularly in association with gynecomastia. We report a rare case of male breast fibromatosis and discuss the diagnostic challenges, surgical decision-making, and reconstructive management. Methods: A 35-year-old male presented with a palpable right breast mass and bilateral grade II gynecomastia. Histopathological and immunohistochemical analyses were performed. Following multidisciplinary evaluation, the patient underwent wide local excision of the lesion with immediate glandular-adipose tissue rearrangement and simultaneous contralateral gynecomastia correction. Results: Ultrasonography demonstrated a hypoechoic lesion of 12 × 11 mm, whereas mammography revealed an irregular mass measuring up to 34 mm. Core needle biopsy showed a fibroblast-rich spindle-cell proliferation with nuclear β-catenin positivity, consistent with desmoid-type fibromatosis. Final histopathology confirmed a 2.5 cm lesion with negative resection margins (minimum margin 5 mm). Immediate reconstruction achieved a satisfactory chest contour and symmetry. No evidence of recurrence was observed during 18 months of follow-up. Conclusions: Breast fibromatosis should be considered in the differential diagnosis of suspicious male breast lesions because radiological findings may closely resemble breast carcinoma. Histopathological confirmation remains essential for appropriate management. In selected patients, immediate glandular-adipose tissue rearrangement may facilitate single-stage defect reconstruction and preservation of chest contour following oncologic excision.

Background: With a peak incidence in young adulthood, desmoid tumors (DTs) often cause pain, loss of function, and diminished quality of life. On the basis of findings from the Phase III desmoid fibromatosis (DeFi) trial, the selective gamma secretase inhibitor nirogacestat was approved by the US Food and Drug Administration (FDA) in November 2023 for the treatment of patients with DT.

Methods: A retrospective, single-institution chart review of patients with DT who initiated nirogacestat therapy over a 14-month period was undertaken. Measured real-world outcomes included radiographic tumor response, patient-reported pain, and toxicities attributable to nirogacestat.

Results: Eleven young adult (YA) patients with DT who received nirogacestat were identified for the study. The median patient age was 26 years. The median duration of therapy at the time of the study was 8 months. RECIST responses included one patient with a partial response (PR), eight with stable disease (SD), and two were deemed radiologically inevaluable. Eight out of nine evaluable patients (88%) demonstrated a reduction in tumor volume and improvement in magnetic resonance imaging (MRI) T2-weighted signal intensity. Nine out of 10 patients who presented with pain (90%) reported rapid improvement. The most common toxicities included diarrhea, nausea, rash, and ovarian dysfunction. Discontinuation of nirogacestat was necessary in one patient due to severe diarrhea. Out of nine female patients, two elected to undergo oocyte cryopreservation prior to starting therapy.

Conclusions: Nirogacestat provided therapeutic benefit in the majority of the YA DT population with rapid and sustained pain relief. The toxicity profile was generally predictable and manageable. The experience expands upon the findings of the DeFi Trial, defining the real-world benefits, toxicities, and supportive care needs.

Desmoid-type fibromatosis of the breast is an uncommon, low-grade mesenchymal neoplasm with benign histologic features, characterized by locally aggressive growth and a notable tendency for local recurrence. Clinical management is challenging owing to frequent positive surgical margins, a propensity for recurrence, and the absence of standardized treatment guidelines. We report the case of a 34-year-old woman who underwent mastectomy for recurrent breast desmoid-type fibromatosis, in whom a heterozygous germline MUTYH (MutY DNA glycosylase) variant was identified through hereditary cancer panel testing. This case highlights the potential value of comprehensive pathologic assessment and selective germline genetic testing in patients with recurrent breast fibromatosis, which may offer further insight into tumor biology and inform individualized management strategies.

Aggressive Fibromatosis (AF) is a rare mesenchymal tumor characterized by nuclear β-catenin positivity. Its exact etiology remains unclear but is thought to be associated with hormonal factors, trauma, or prior surgery. Clinically, AF is uncommon and demonstrates nonspecific imaging features, frequently complicating preoperative diagnosis. This is particularly true for intra-abdominal AF presenting with atypical features, which can be easily mistaken for other abdominal space-occupying lesions. Herein, we report two rare cases of primary intestinal AF, one of which was complicated by tumor rupture and subsequent intra-abdominal abscess formation. Through an integrated analysis of clinical presentation, imaging findings, and pathological results, this report discusses the diagnostic considerations and management strategies for AF.