A Nationwide Analysis of Head and Neck Fibromatoses

Background: Head and neck fibromatoses (HNFs) are a rare, diverse group of soft tissue tumors characterized by an abnormal proliferation of fibroblasts. Available literature on these tumors is limited to case reports and small single-institutional studies.

Objective: We aim to provide demographic, socioeconomic, tumor-related, and treatment characteristics of HNFs.

Design: Retrospective cohort analysis using the National Cancer Database (NCDB).

Methods: The NCDB was queried for fibromatosis-related histologic codes located within the head and neck region. Various factors were analyzed. Univariate and multivariate survival analyses were performed.

Results: Between 2004 and 2016, 130 patients were included in the analyses. Average age was 57.4 years old with a predominance of White (83.6%) males (61.5%). Non-desmoid HNFs accounted for 60%-70% of the tumors. The salivary gland was the most common location (38.5%) and more than half of the tumors were high grade. The majority were treated surgically (90.8%) and 25% had positive margins. Mean and median overall survival (OS) were 98.9 and 135.4 months, respectively. Surgery is associated with better OS than nonsurgical alternatives. Addition of adjuvant treatments was not associated with differences in survival.

Conclusion: In the largest study to date, we describe demographic, socioeconomic, tumor-related, and treatment patterns of patients with this rare disease. These tumors are most frequently present in middle-aged males with high-grade histology. Most are treated surgically and positive surgical margins are common. Surgery has better OS than nonsurgical alternatives. While adjuvant radiation has become more common, we found no difference in survival compared to surgery alone.

Fibromatosis or desmoid tumors are rare benign fibroblastic lesions that are rarely present in the head and neck regions. When they do occur in these regions, however, they tend to be aggressive toward the surrounding tissue and be associated with heavy morbidity and mortality. We report the case of a 26-year-old Tunisian female who presented with acute obstructive dyspnea and a 3-week history of cervical swelling. The swelling was initially only located in the left submandibular area, it then gradually extended to all the anterior cervical supra- and infrahyoid regions causing a clinical presentation resembling that of obstructive dyspnea, the patient was admitted, and an emergency tracheotomy was performed. Tissue samples were taken, pathological analysis revealed an aggressive case of fibromatosis. The patient was treated with corticosteroids and antihormonal therapy, the fibrous mass shrunk considerably allowing the removal of the tracheotomy cannula, no tumor recurrence was noted during the observation period. Due to the rarity of this disease, especially in the cervical region, there are no therapeutic guidelines available.

Fibromatosis, or desmoid tumour, is characterized by excessive and infiltrative proliferation of connective tissue originating from aponeurotic muscle structures. Mammary fibromatosis is rare in humans and animals and its precise aetiology is unknown. A 10-year-old mixed-breed female dog developed a mass in the right cranial thoracic mammary gland (M1) and underwent lumpectomy. The mass was firm, with an irregular surface and distinct limits. Microscopically, it was a neoplastic proliferation of fusiform cells with low atypia, interspersed with abundant dense collagenous tissue, confirmed by histochemical staining with Gomori’s trichrome and Masson’s trichrome and immunopositivity for vimentin and smooth muscle actin, confirming mammary fibromatosis. Mammary fibromatosis in dogs needs further studies to elucidate its clinical, epidemiological and aetiopathogenic aspects.

Desmoid tumor (DT) is a rare fibroblastic soft-tissue neoplasm that is characterized by local aggressiveness but no metastatic potential. Although the prognosis is relatively favorable, the unpredictable disease course and infiltrative growth lead to significant impairments and morbidity. Aberrant activation of Wnt/?-catenin signaling has been well-established in the pathogenesis of sporadic DT and familial adenomatous polyposis (FAP) or Gardners syndrome-associated DT, suggesting therapy targeting this pathway is an appealing treatment strategy. However, agents against this pathway are currently in their preliminary stages and have not yet been implemented in clinical practice. Increasing studies demonstrate activation of the Notch pathway is closely associated with the development and progression of DT, which provides a potential alternative therapeutic target against DT. Early-stage clinical trials and preclinical models have indicated that inhibition of Notch pathway might be a promising treatment approach for DT. The Notch signaling activation is mainly dependent on the activity of the ?-secretase enzyme, which is responsible for cleaving the Notch intracellular domain and facilitating its nuclear translocation to promote gene transcription. Two ?-secretase inhibitors called nirogacestat and AL102 are currently under extensive investigation in the advanced stage of clinical development. The updated findings from the phase III randomized controlled trial (DeFi trial) demonstrated that nirogacestat exerts significant benefits in terms of disease control and symptom resolution in patients with progressive DT. Therefore, this review provides a comprehensive overview of the present understanding of Notch signaling in the pathogenesis of DT, with a particular emphasis on the prospective therapeutic application of ?-secretase inhibitors in the management of DT.

Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64-1.40), p = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), p = 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.