1477PDPrognosis of desmoid tumours initially managed with surveillance only at all anatomical locations

The aim of this study is to analyse the need and indications for treatment in desmoid patients initially managed with surveillance only. Patients with a desmoid tumour at any anatomical location diagnosed between 1998 and 2016 were selected from a prospectively maintained database. Differences between patient groups were analysed with independent t-tests or Chi-square tests. Inverse univariate cox proportional hazard regression analyses were conducted to assess factors associated with start of treatment, tumour behaviour and pain. A total of 168 patients initially managed with surveillance only were identified. The tumours were located in…

Wnt signaling is implicated in tumor cell de-differentiation and cancer stem cell function. Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human Frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands. This trial evaluated ipafricept in patients with solid tumors. A 3+3 design was used; ipafricept was given intravenously every 3 weeks. Objectives were determination of dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy. 26 patients were treated in 7 dose-escalation cohorts (0.5, 1, 2.5, 5, 10, 15 and 20 mg/kg). Most common related Grade 1 and 2 adverse events (AEs; ³20% of patients) were dysgeusia, decreased appetite, fatigue, and muscle spasms. Ipafricept-related Grade 3 TEAEs included hypophosphatemia and weight decrease (1 subject each, 3.8%). Ipafricept half-life was ~4 days, and had low incidence of anti-drug antibody formation (7.69%) with no impact on drug exposure. Six patients had _-C-terminal telopeptide (_-CTX) doubling from baseline, which was reversible. PD modulation of Wnt pathway genes in hair follicles occurred ³2.5 mg/kg. Two desmoid tumor and a germ cell cancer patient experienced stable disease for >6 months. Ipafricept was well tolerated, with RP2D of 15 mg/kg Q3W. Prolonged SD was noted in desmoid tumor and germ cell cancer patients.

Pre-emptive transplantation is a well-established practice for certain types of end-organ failure such as in the use of kidney transplantation. For irreversible intestinal failure, total parenteral nutrition (TPN) remains the gold standard, due to the suboptimal long-term results of intestinal transplantation. As such, the only role for pre-emptive transplantation, if at all, will be for patients identified to be at high risk of complications and mortality while on definitive long-term TPN. In these patients, the timing of early listing and transplantation could become life-saving, taking into account that mortality on the waiting list is still the highest for intestinal candidates. The development of simulation models or pre-transplant scoring systems could help in selecting patients based on potential outcome on TPN or with transplantation, and recent reports from high-volume centers identify few underlying pathologic conditions and some TPN complications as at higher risk of increased morbidity and mortality. A pre-emptive transplant could be used as a rehabilitative procedure in a well-selected case-by-case scenario, among TPN patients at risk of liver failure, repeated central line infections, mesenteric infarction, short bowel syndrome (SBS) <50 cm or with end stoma, congenital mucosal disease, desmoid tumors: These conditions must be carefully evaluated, not to underestimate the clinical stage nor to over-estimate the impact of a temporary situation. At the present time, diseases with a variable and unpredictable course, such as intestinal dysmotility disorders, or quality of life and financial issues are still far from being considered as indications for a pre-emptive transplant.

We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0-96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5-21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation.

In the case report, a 39-year-old man presented with progressive chest wall pain. Computed tomography (CT) showed an approximately 46 _ 13mm soft-tissue mass between the inside of the fifth and sixth rib on the right side. The entire mass was excised and an AF was confirmed based on histopathology. Four months after surgery, magnetic resonance imaging(MRI) showed a soft-tissue mass in surgical areas and biopsy confirmed local recurrence. Therefore, Tomotherapy was administered. However, two months later, an (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography combined with CT (PET-CT) revealed the presence of an FDG-avid mass in the area of local recurrence. Genetic testing reported the presence of a p.T41A mutations on the CTNNB1 gene, which predicted that he is sensitive to the COX-2 inhibitor celecoxib. The tumor regressed rapidly after the application of celecoxib. Within the 20-month follow-up period, the patient showed remarkable regression without any signs and symptoms. Our case report provides further evidence for the efficacy of celecoxib in AF with CTNNB1 gene mutations. To our knowledge, this is the first report of AF treated with celecoxib under the guidance of the genetic testing. However, further studies are required.

The present retrospective analysis aimed to determine prognostic factors leading to recurrence. Between 2000 and 2014, 114 patients with aggressive fibromatosis were treated surgically at BG_University Hospital Bergmannsheil (Bochum, Germany). Primary tumors were resected with negative margins (R0) in 50 patients (68%) and with microscopically positive margins (R1) in 28 patients (25%). In addition, tumors in 12 patients (7%) were resected with macroscopically positive margins at the initial surgical procedure. The rates of recurrence_free survival (RFS) after 5 years were 68.8% [95% confidence interval (CI), 53.5_79.9%] in patients with R0_resected primary tumors and 34.1% (95% CI, 19.9_48.9%) in patients with R1/R2_status (P=0.001). Narrow and wide clear margins within the R0_group were not associated with significantly different outcomes. Adjuvant radiation, tumor site and patient age were not associated with a significant alteration of RFS. The current results suggest that the attainment of microscopically negative surgical margins at the initial surgical treatment is associated with a significantly improved prognosis.