Tailoring Desmoid Treatment

Desmoid-type fibromatosis (DF) is a rare disease, also known as aggressive fibromatosis or desmoid tumor. DF is characterized by infiltrative growth with a tendency toward local recurrence but an inability to metastasize. The incidence of DF is low. The pathogenesis of this rare disease is not fully understood. Genetic mutations seem to be major factor, in addition to hormonal influences. The treatment options for DF are dependent on the localization of the tumor. The classical treatment of extra-abdominal and abdominal DF implies primary surgery, with radiotherapy on indication. During the past decade, this advice switched based on accumulating evidence to active surveillance and in case of progressive disease surgery, radiotherapy or systemic treatment based on localization. The natural behavior of DF ranges from spontaneous regression to rapid invasive growth. It is challenging to predict the behavior of a tumor in an individual. This thesis is about tailoring the treatment of DF. Current medical care is patient oriented, with a trend toward individualized treatment strategies. This thesis focusses on changes in epidemiology, treatment modalities and the ability to predict tumor behavior

Time Trends in the Incidence and Treatment of Extra-Abdominal and Abdominal Aggressive Fibromatosis: A Population-Based Study

Background: Aggressive fibromatosis (AF) is a locally infiltrating soft-tissue tumor. In a population-based study in the Netherlands, we evaluated time trends for the incidence and treatment of AF. Methods: In PALGA: Dutch Pathology Registry, all patients diagnosed between 1993 and 2013 as having extra-abdominal or abdominal wall aggressive fibromatosis were identified and available pathology data of the patients were evaluated. Epidemiological and treatment-related factors were analyzed with χ2and regression analysis. Results: During the study period, 1134 patients were identified. The incidence increased from 2.10 to 5.36 per million people per year. Median age at the time of diagnosis increased annually by B 0.285 (P = 0.001). Female gender prevailed and increased over time [annual odds ratio (OR) 1.022; P = 0.058]. All anatomic localizations, but in particular truncal tumors, became more frequent. During the study period diagnostic histological biopsies were performed more often (annual OR 1.096; P < 0.001). The proportion of patients who underwent surgical treatment decreased (annual OR 0.928; P < 0.001). When resection was preceded by biopsy, 49.8 % of the patients had R0-resection versus 30.7 % in patients without biopsy (P < 0.001). Conclusions: In this population-based study, an increasing incidence of extra-abdominal and abdominal-wall aggressive fibromatosis was observed. The workup of patients improved and a trend towards a nonsurgical treatment policy was observed

Multifocal occurrence of extra-abdominal desmoid type fibromatosis – A rare manifestation. A clinicopathological study of 6 sporadic cases and 1 hereditary case

Desmoid-type fibromatosis, also called desmoid tumor, is a locally aggressive myofibroblastic neoplasm that usually arises in deep soft tissue with significant potential for local recurrence. It displays an unpredictable clinical course. β-Catenin, the genetic key player of desmoid tumors shows nuclear accumulation due to mutations that preve

Isolated limb perfusion using tumour necrosis factor α and melphalan in patients with advanced aggressive fibromatosis

Background: Aggressive fibromatoses (desmoid tumours) may be locally aggressive, but do not metasta-size. Although a conservative approach is advocated for most patients, pain and functional impairment are indications for active treatment. Tumour necrosis factor (TNF) α and melphalan-based isolated limb perfusion (TM-ILP) is a limb-saving treatment modality for soft tissue tumours. This study reports the results of TM-ILP treatment in patients with aggressive fibromatosis.Methods: Institutional databases of three European centres were searched. All patients who received TM-ILP treatment for aggressive fibromatosis between 1990 and 2012 were included. Before therapy, the patients were discussed at multidisciplinary tumour board meetings.Results: Twenty-five patients received 28 TM-ILP treatments. The median age of patients was 28 (i.q.r. 19-34) years and median hospital stay was 8 (7-12) days. Median follow-up was 84 (34-114) months. A complete response was achieved after two TM-ILP treatments, and a partial response after 17 treatments in 16 patients. Stable disease was reported after eight treatments in seven patients, including a patient with stable disease after the first treatment and progression after the second TM-ILP. Toxicity was modest after most treatments; Wieberdink grade IV (extensive epidermolysis, and threatening or manifest compartment syndrome) was seen after two TM-ILP treatments. Systemic leakage was reported after one treatment, but did not lead to systemic toxicity. Functional outcome was good; 16 patients had no physical limitations, and six patients had some limitations but did not need medical aids. Amputation was prevented in all but three patients.Conclusion: TNF-α-based ILP is effective in patients with aggressive fibromatosis