Quality of life and tumor location in patients with desmoid tumors: Data from the desmoid tumor research foundation natural history study

Desmoid tumors (DTs) are sarcoma, known to invade surrounding tissues, compromising organ function and complications. As few as 5 per 1 million people are diagnosed with DTs annually, which may be an underestimate of the actual affected population due to difficulty in correctly diagnosing the disease. To improve awareness of DTs and better inform treatment development, DTRF, in partnership with the NORD, launched the DTRF patient registry and natural history study. Here, we describe patient demographics, tumor location, and QOL in registry patients. The registry launched September 2017 and contains 15 surveys covering diagnostics, disease, treatment, care management, and quality of life. As of January 2019, 357 patients have completed 2,371 surveys. Registry participants are mostly white (88%, 313/357), female (81%, 277/343), and reside in 27 countries with 80% (285/357) US-based. Median age at diagnosis is 33 and the time from onset of symptoms to diagnosis was more than 1 year for 54% (189/352). DT location was reported for 119 respondents at time of data collection. Most prevalent locations were joint /extremities (39%, 47/119), intra-abdominal (24%, 28/119), and chest wall (24%, 29/119). Multiple locations were indicated for 22% (26/119). QOL reported as very good or excellent ranged from 28% to 60%, depending on DT location. Patients with DTs have varied QOL and tumor locations. Data collection through the study is ongoing.

Fibromatoses with onset in infancy and childhood are characterized with higher cellularity and more aggressive growth. The mainstream management of aggressive fibromatosis (AF) is surgical removal with microscopically lesion-free margins. In advanced cases, radical surgery can lead to function loss and disfigurement. Hence, early diagnosis and management can avoid complications. Although uncommon (two to four cases per million per year are reported), approximately 25 percent of AF incidents occur in children younger than 15 years of age. Pediatric dentists are likely to be the first practitioners to encounter new cases of AF in younger populations and should have knowledge and understanding of this entity. The purpose of this report is to present a rare case of AF affecting the mandible of a young patient.

A 26-year-old lady presented with a palpable mass of one and half year’s duration, on the left side of her abdomen. It was painless but mild dragging sense was present. She had no history of fever, vomiting or any other complaint. She noticed the mass for the first time during her second trimester of third pregnancy. She had no history of previous surgery. Her bladder and bowel habits were normal. On general examination, patient was afebrile, vitals were stable. Mild pallor was present. Abdominal examination revealed a fairly globular non-tender mass measuring 20 cms across, occupying left flank and umbilicus. It was soft to firm in consistency and immobile. FNAC reported as benign spindle cell tumour. A contrast-enhanced computed tomography (CT) scan revealed a large heterogeneously enhancing well defined soft tissue intra-abdominal mass in left flank and left retroperitoneum with invasion of left flank muscles suggestive of benign soft tissue tumour with minimal ascites. At exploratory laparotomy, a mass of around 30 cm x 25 cm was present extending from anterolateral abdominal wall into the retroperitoneum with multiple feeding vessels present, without any solid organ adherence. The mass was excised completely. Gross examination of the cut section reveals firm whorled mass located within surrounded by skeletal muscle. Histopathological examination revealed an intrabdominal fibromatosis with densely collagenised stroma and dilated vessels with myxoid change. Microscopic picture of the tissue showed fish in a stream pattern and stellate cells. There were no intraoperative or postoperative complications. Patient was discharged on 8th postoperative day. Follow up till 2 years bears no evidence of recurrence.

Desmoid tumor represents an intermediate grade neoplasm with a striking predilection for locally invasive growth and recurrence following resection. More effective, well-tolerated non-surgical treatment options are needed. Current approaches: If feasible, watchful waiting is the preferred approach, 20-30% spontaneous regression. In situations where treatment is indicated, the following approaches are utilized:vSurgery is the primary approach if minimal morbidity is anticipated, Medical therapies, Cytotoxic drugs, Tyrosine kinase inhibitors, Hydroxyurea, Gamma secretase inhibitors. mTOR Inhibitor Rationale: Desmoid tumor is well-known to be associated with deregulation of the APC/beta-catenin pathway, Deregulation of the mTOR cell proliferation/survival pathway may play an important role in tumor biology when the APC/beta-catenin pathway is disrupted, The mTOR inhibitor sirolimus is attractive as a potential targeted therapy for desmoid tumor, Well-tolerated in children and young adults, Can be given orally in tablet or liquid formulation.

Recently, targeted therapies are being explored in desmoid-type fibromatosis (DTF). Unfortunately, effective treatment is still hampered by the limited knowledge of the molecular mechanisms that prompt DTF tumorigenesis. Many studies focus on Wnt/beta-catenin signaling, since the vast majority of DTF tumors harbor a mutation in the CTNNB1 gene or the APC gene. The established role of the Wnt/beta-catenin pathway in DTF forms an attractive therapeutic target, however, drugs targeting this pathway are still in an experimental stage and not yet available in the clinic. Only few studies address other signaling pathways which can drive uncontrolled growth in DTF such as: JAK/STAT, Notch, PI3 kinase/AKT, mTOR, Hedgehog, and the estrogen growth regulatory pathways. Evidence for involvement of these pathways in DTF tumorigenesis is limited and predominantly based on the expression levels of key pathway genes, or on observed clinical responses after targeted treatment. No clear driver role for these pathways in DTF has been identified, and a rationale for clinical studies is often lacking. In this review, we highlight common signaling pathways active in DTF and provide an up-to-date overview of their therapeutic potential.

Letter to the editor