The GRAFITI trial: a nationwide prospective clinical trial on active surveillance in patients with non-intraabdominal desmoid-type fibromatosis [Article in German]

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This study aimed to retrospectively review the clinical data, management protocols, clinical outcomes, and literature review of patients diagnosed with head and neck fibromatoses. This case series aims to present and discuss seven cases of rare head and neck fibromatosis. The study design involves retrospective analysis of medical records, radiological imaging, and histopathological reports of the included cases. Ethical approval was obtained from the relevant Institutional Review Board. The results of the study reveal that individuals diagnosed with fibromatosis had a wide age range, starting from 6 to 58 years, with the median age being 44.3 years. Out of the 8 patients, 5 (62.5%) were females and 3 (37.5%) were males. The maxilla was found to be the most common subsite of origin in the head and neck area, followed by the masseter and temporal fossa. At the time of diagnosis, 2 (25%) patients were found to have unresectable disease. Multidisciplinary management therapies, including surgery, chemotherapy, hormonal, targeted therapy, and radiotherapy, were used. Out of the 6 patients who underwent surgery, 5 (83.3%) experienced tumor recurrence. In conclusion, the retrospective analysis underscores the complexity of managing fibromatoses of the head and neck region; complete tumor resection is not achievable always due to the inherent challenges, complex anatomy, and proximity of vital structures in the head and neck. Adjuvant strategies including radiotherapy, chemotherapy, and hormonal therapy have demonstrated efficacy in disease management. The rarity of these tumors necessitates the development of standardized treatment protocols to guide clinical practice effectively. Moving forward, collaborative efforts are crucial to enhance our understanding of fibromatoses and refine therapeutic strategies for improved patient outcomes.

INTRODUCTION AND IMPORTANCE: Tumours arising from previous sites of appendicectomy are a rare phenomenon. There have been few documented cases in literature but for the most part, it is a rare occurrence that needs further investigation. CASE PRESENTATION: A 20-year-old male presented to our outpatient with a large mass in his right upper abdomen for 2 months and a history of an appendicectomy done in an outside hospital 4 years prior. CLINICAL DISCUSSION: After regular investigations, the tumour was resected with adequate margins. On immunohistochemistry, the specimen was said to be of a desmoid fibromatosis. The exact aetiology of the disease cannot be determined unless we get a thorough analysis of the appendix specimen. CONCLUSION: This paves the way to the learning curve, which is that we must ensure proper patient follow-ups with relevant histopathological reports to ensure complete and comprehensive care to the patient.

BACKGROUND/AIM: Desmoid tumors (DTs), or aggressive fibromatosis, are rare neoplasms arising from connective tissue, frequently exhibiting local invasiveness. The limited treatment options and high recurrence rates of DTs highlight the need for novel therapeutic strategies. This study investigated the efficacy of chlorhexidine dihydrochloride (CD) in inhibiting the growth of DTs and colorectal cancer (CRC). MATERIALS AND METHODS: A mouse model with Apc mutations, specifically Apc1638N/+, was generated to study DTs. DT cells (Apc1638N+) (DTA) were collected from the mice for in vitro experiments. DTA were treated with CD, along with a CRC cell line (HCT-116), and tumor organoids derived from Apc1638N/+ mice. The effects of CD were assessed through cell viability assay (WST assay), colony formation assay, and cell migration assay. We tested the induction of cell apoptosis through caspase 3/7 activity assays and immunoblot analysis of cleaved-caspase 3 and cleaved-PARP1. Additionally, CD was tested for its anti-tumor efficacy using an in vivo CRC xenograft model with the HCT-116 cell line. RESULTS: CD significantly inhibited the viability, migration, and colony formation of DTA and CRC cells. It remarkably decreased the tumor growth in organoids derived from intestinal tumor cells in the Apc1638N/+ mouse model. Furthermore, CD showed anti-tumor effects in an in vivo CRC xenograft model using the HCT-116 cell line. CONCLUSION: CD represents a promising therapeutic strategy for treating both DTs and CRC.

PURPOSE: Three prospective observational studies (Italy, the Netherlands, France) on active surveillance (AS) in patients with extra-abdominal desmoid-type fibromatosis (DTF) support AS as a frontline approach. Identifying prognostic factors for the failure of AS will help determine the strategy. The aim of this study was to investigate the prognostic impact of clinical and molecular variables in a larger series. EXPERIMENTAL DESIGN: Data available as of January 31st, 2024, from the three studies, in which patients were followed for ≥3 years, were pooled. Patients ≥18 years old, with primary sporadic DTF and with CTNNB1 mutations available, were eligible. The primary study endpoint was treatment-free survival (TFS). Secondary endpoints included the incidence of RECIST progression, spontaneous RECIST regression and regression post-RECIST progression. RESULTS: Two hundred and eighty-two patients (n = 282) with a median follow-up of 53 months (IQR, 39-63) were included. Three-year and five-year TFS were 67% and 66%, crude cumulative incidences (CCI) of RECIST progression were 33% and 34%, of RECIST regression 26% and 34% and of regression post-RECIST progression 33% and 38%. In multivariable analysis, larger tumour size, mutation type, tumor locations were associated to lower TFS. The specific mutation (S45F), larger tumor size, and extremity and trunk location were all associated with a lower probability of spontaneous RECIST regression. CONCLUSIONS: This study confirms that spontaneous regression occurs in a significant proportion of patients and that two-thirds are treatment-free at 5 years. Initial tumor size, CTNNB1 mutation, and location should be factored into the initial decision-making process.

AIMS: Mutations affecting exon 3 of the β-catenin (CTNNB1) gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define clinically relevant tumour subtypes within certain entities, such as endometrioid carcinoma. In diagnostics, β-catenin immunohistochemistry is widely used as a surrogate for CTNNB1 mutations. Yet, it is often difficult to assess in practice, given that the characteristic nuclear translocation may be focal or hard to distinguish from the spillover of the normal membranous staining. METHODS: We therefore examined lymphoid enhancer-binding factor 1 (LEF1) immunostaining, a nuclear marker of WNT activation that serves as a potential surrogate for CTNNB1 mutations. RESULTS: In a cohort of endometrial carcinomas with known mutation status (n=130) LEF1 was 85% accurate in predicting CTNNB1 mutation status (64% sensitivity, 90% specificity) while β-catenin was 76% accurate (72% sensitivity; 77% specificity). Across a variety of entities characterised by CTNNB1 mutations as putative drivers, we found diffuse and strong expression of LEF1 in 77% of cases. LEF1 immunostaining proved easier to interpret than β-catenin immunostaining in 54% of cases, more difficult in 1% of cases and comparable in the remaining cases. CONCLUSION: We conclude that LEF1 immunostaining is a useful surrogate marker for CTNNB1 mutations. It favourably complements β-catenin immunohistochemistry and outperforms the latter as a single marker.