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Posters, Abstracts & Presentations

DTRF encourages researchers to send us summaries about their work with desmoid tumors. Those interested should contact us with this information. View DTRF-funded studies here.

2017 DTRF Research Workshop Abstracts and Presentations

  • David Kirsch, MD, PhD, Barbara Levine University Professor and Vice Chair for Basic & Translational Research, Department of Radiation Oncology Professor, Department of Pharmacology & Cancer Biology, Duke University. 
    “Using radiation therapy to treat desmoid tumors.”  Abstract   |  Presentation

 

  • Tom van Cann, MD, Medical Oncologist, KU Leuven.
    “Systemic treatment preferences for patients with advanced desmoid-type fibromatosis in Europe.”  Abstract

 

  • Milea J.M. Timbergen, MD, PhD candidate, Erasmus Medical Center.
    “Results of the interim analysis of the Dutch GRAFITI study.”  Abstract  |  Presentation

 

  • Breelyn Wilky, MD, Assistant Professor in Hematology/Oncology, University of Miami Sylvester Comprehensive Cancer Center.
    “Mutation phenotypes and their responses to chemotherapy.”  

 

  • Chiara Colombo MD, Surgical Oncology, Fondazione IRCCS- Instituto Tumori di Milano.
    β -catenin in Desmoid-Type Fibromatosis: deep insights on the role of T41A and S45F mutations on protein structure and gene expression.”  

 

  • Danielle Braggio, PhDPost-Doctoral Researcher, Ohio State University.
    “Autophagy inhibition overcomes sorafenib resistance in S45F-mutated desmoid tumors.”  Abstract  |  Presentation

 

  • Yoshihiro Nishida, MD, PhD, Associate Professor, Nagoya University Graduate School of Medicine.
    “Effects of mechanical forces on the cell behavior of desmoid-type fibromatosis.”  Abstract

 

  • Kris Vleminckx, PhD, Professor, Department of Molecular Biomedical Research Unit of Developmental Biology VIB, Ghent University.
    “Therapeutic target identification in a Xenopus model for desmoid tumor formation – an update.”  Abstract

 

  • Gerlinde Wernig, MD, Assistant Professor of Pathology, Stanford University.
    “Unifying mechanism of different fibrotic diseases.”  

 

  • Sant Chawla, MD, FRACP, Medical Director, Sarcoma Oncology Research Center.
    “Designing new clinical trials in desmoid tumor.”  Presentation

 

  • Steve Horrigan, PhD, Chief Scientific Officer, Beta Cat Pharmaceuticals
    “Tegavivint (BC2059) – A new way of attacking beta-catenin driven disease.”

 

  • Danielle Braggio, PhD, Post-Doctoral Researcher, Ohio State University
    “Tegavivint (BC2059) studies in desmoid cell lines.”

 

  • Benjamin Alman, MD, Professor and Chair, Department of Orthopedic Surgery, Duke University.
    “Tegavivint (BC2059) studies in Apc(+)/Apc(1638N) genetic mouse model of aggressive fibromatosis.”  

 

  • Casey Cunningham, MD, Chief Medical Officer, Beta Cat Pharmaceuticals.
    Synopsis of a Planned Phase 1/2 Study of Tegavivant (BC2059) in desmoid tumors.”  Abstract

 

  • Benjamin Alman, MD, Professor and Chair, Department of Orthopedic Surgery, Duke University.
    “Introduction and report on Collaboration for a Cure project.”  Presentation

 

  • Kelly Mercier, PhD, Research Scientist in Metabolomics, RTI International.
    “A metabolomics pilot study on desmoid tumors and novel drug candidates.”  Abstract  

 

  • Gary Schwartz, MD, Chief, Division of Hematology/Oncology, Columbia University.
    A systems biology approach to the identification of new treatments for patients with soft tissue sarcomas including desmoid tumors.”  Abstract  |  Presentation

 

  • Aaron Weiss, DO, Assistant Clinical Professor of Pediatrics, Maine Medical Center.
    Development of a DTRF-sponsored virtual tumor board.”  Abstract  |  Presentation

 

  • Kelly Mercier, PhD, Research Scientist in Metabolomics, RTI International.
    “DTRF Natural History Study and patient registry launch and update.”  Abstract  |  Presentation

2017 DTRF Patient Meeting Abstracts and Presentations

2017 CTOS Meeting

PAPERS

 

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

Winan J. van Houdt, MD, PhD, MSc1; Alisha Patel1; Robin L. Jones2; Myles J. Smith1; Aisha Miah3; Charlotte Benson2; Shane Zaidi; Christina Messiou4; Eleanor Moskovic4; Dirk C. Strauss1; Andrew J. Hayes1; Olga Husson2; Winette van der Graaf2

1 Department of Surgical Oncology, The Royal Marsden Hospital, London, United Kingdom; 2 Department of Medical Oncology, the Royal Marsden Hospital, London, United Kingdom; 3 Department of Clinical
Oncology, the Royal Marsden Hospital, London, United Kingdom; 4 Department of Radiology, the Royal Marsden Hospital, London, United Kingdom

 

An update on the management of sporadic desmoid-type fibromatosis: A European consensus initiative between Sarcoma Patients Euronet (SPAEN) and European Organisation for Research and Treatment of Cancer (EORTC)/ Soft Tissue and Bone Sarcoma Group (STBSG)

Bernd Kasper, MD, PhD1; Christina Baumgarten2; Jesica Garcia2; Sylvie Bonvalot3; Rick Haas, MD, PhD4;
Florian Haller5; Peter Hohenberger1; Nicolas Penel6; Christina Messiou7; Winette van der Graaf8; Alessandro Gronchi9
1 Interdisciplinary Tumor Center, Mannheim University Medical Center, Mannheim, Germany; 2 Sarcoma Patients EuroNet (SPAEN), Wölfersheim, Germany; 3 Department of Surgical Oncology, Institut Curie, PSL University, Paris, France; 4 Department of Radiotherapy, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; 5 Institute of Pathology, Friedrich Alexander University Erlangen, Erlangen, Germany; 6
Department of Medical Oncology, Centre Oscar Lambret, Lille, France; 7 Radiology, The Royal Marsden Hospital, London, United Kingdom; 8 Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom; 9 Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

 

Autophagy inibition overcomes sorafenib resistance in CTNNB1 mutant S45F desmoid tumors

Danielle Braggio, PhD1; David Koller2; Feng Jin3; Nanda Siva4; Abeba Zewdu1; Gonzalo Lopez; Kara Batte1; Lucia Casadei, PhD1; Meng Welliver3; Anne Strohecker1; Raphael Pollock2; Dina Lev5

1 Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; 2 Department of Surgery, The Ohio State University, Columbus, OH, USA; 3 Radiation Oncology Department, The Ohio State University, Columbus, OH, USA; 4 Department of Chemical and Biomedical Engineering, West Virginia University Statler College of Engineering and Mineral Resources, Morgantown, WV, USA; 5 Surgery B’Sheba Medical Center, Tel Aviv, Israel

 

 

POSTERS

IDENTIFICATION OF NOVEL SURFACE MARKERS FOR TUMOR-STROMA INTERACTION STUDIES IN DESMOID TUMORS
Mushriq Al-Jazrawe, Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, CANADA; Q. Wei, S. Xu, J. Loree, R. Poon, Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, CANADA; B. Alman, Duke University, Durham, North Carolina, USA

Objective: The role of stromal fibroblasts in promoting tumor growth and invasion has been underexplored in soft tissue sarcoma partly due to lack of reliable markers that differentiate between the neoplastic and non-neoplastic mesenchymal cells. Desmoid tumors (DT), characterized by proliferating and locally invasive fibroblastic cells, are driven by mutations that increase beta-catenin (CTNNB1) levels. We aimed to identify surface markers that can distinguish between the neoplastic and non-neoplastic fibroblastic cells within DT and investigate the tumor-stroma interactions that maintain the neoplastic phenotype.Methods: Multiple single cell expansions were established from each DT sample. CTNNB1 mutation status of each colony was identified by Sanger sequencing. Mutant and non-mutant colonies were analyzed by flow cytometry for the expression of 368 surface proteins. Candidate surface markers were validated by fluorescence-activated cell sorting (FACS) and double immunofluorescence. Differential secretome analysis was conducted by antibody arrays and by gene expression profiling. Transwell permeable supports were utilized for mutant-stromal fibroblast co-cultures in cell interaction studies.Results: We detected both mutant and non-mutant colonies derived from primary DT cultures. The mutant colonies expressed CD142 and CD252 while the non-mutant colonies expressed podoplanin (PDPN). FACS using these surface markers identified the mutant subpopulation in heterogeneous DT samples, including specimens that previously appeared as “wildtype.” In DT tissues, CD142 and CD252 expressing cells correlated with higher CTNNB1 staining and exhibited a distinct spatial distribution compared to PDPN expressing cells. Our secretome profiling revealed several candidate soluble factors for autocrine or paracrine signaling. CTHRC1 is one of the secreted proteins highly produced by the mutant population. Treatment with recombinant CTHRC1 increased cell proliferation while treatment with a CTHRC1 neutralizing antibody decreased proliferation.Conclusion: We have identified novel surface markers that can be utilized to rapidly and sensitively detect the mutant population within DT samples. Isolation of the mutant and non-mutant subpopulations allows for the detection of secreted factors that may be involved in tumor-stroma communication, which can be targeted therapeutically. The differential expression of these surface proteins and secreted factors suggests that they may also be used as clinical biomarkers.

 

COMBINATION CHEMOTHERAPY FOR AGGRESSIVE FIBROMATOSIS: PRELIMINARY RESULTS FROM BETA-CATENIN INHIBITOR, DEXAMETHASONE, AND FOCAL ADHESION KINASE INHIBITOR
Sean Ryan, Orthopaedics, Duke University Hospital, Durham, North Carolina, USA
V. Puviindran, P. Nadesan, Y. Kwak, B. Alman, Orthopaedics, Duke University Hospital, Durham, North Carolina, USA

Objective: Aggressive fibromatosis (AF), commonly referred to as Desmoid tumor, is a locally aggressive lesion often treated with surgical resection, however, high local recurrence rates generate continued interest in chemotherapeutic options. Prior authors have investigated different therapies through both in vivo and in vitro studies with variable results; however, there is a paucity of literature available on multi-drug regimens. Given the infrequent occurrence of these aggressive lesions and lack of funding to generate novel chemotherapeutics, the majority of research focuses on using current FDA approved medications in hopes for a therapeutic response in AF. At the investigating institution, a prior drug screen has returned numerous medications that show promising activity in AF. Therefore, we sought to investigate various regimens from the drug screen to determine the utility of combination therapy in AF.Methods: Apc+/Apc1638N mice, which develop AF lesions, were treated with either monotherapy or dual therapy with BC2059 (a beta catenin inhibitor), Focal Adhesion Kinase (FAK) inhibitor, and Dexamethasone. The mice were sacrificed at 6 months following treatment and tumor number and volume analyzed. AF tumors were then analyzed through immunohistochemistry (IHC), western blot, and real time PCR for markers of proliferation and apoptosis (KI67 and caspase), as well as beta catenin and downstream protein activity. Human cell cultures undergoing the same treatment combinations were then performed. Funding for this study was provided by the Desmoid Tumor Research Foundation.Results: Preliminary results from gross tumor analysis from Apc+/Apc1638N mice has shown significant decrease in tumor number with BC2059 mono-therapy compared to control (p=0.0004). Mon-therapy with FAK inhibitor and Dexamethasone trended toward diminished tumor burden, however, these results were not significant. Combination therapy with BC2059 and dexamethasone, as well as FAK inhibitor and dexamethasone showed significant decreased tumor number compared to control (p<0.0001) [figure 1]. Average tumor volume showed a similar response to treatment with combination therapy, with dual treatment outperforming control and monotherapy. These differences, however, were not significant [figure 2]. Protein, RNA, and human cell culture treatment analysis are currently being performed.Conclusion: Desmoid tumors are locally aggressive lesions, and due to high local recurrence rates, there is a need for effective chemotherapeutic options. Based on the preliminary results of this study, combination therapy with FAK inhibitors, Dexamethasone, and BC2059 (a beta catenin inhibitor) appear to be effective treatment options, which may warrant further evaluation with phase II clinical trials. Further analysis on these tumors will provide more insight into the therapeutic effects of these medications.

 

METHOTREXATE PLUS VINORELBINE (MTX/VBL) CHEMOTHERAPY FOR THE MEDICAL MANAGEMENT OF DESMOID FIBROMATOSIS (DF)
Sally Burtenshaw, R. Gladdy, A.M. Olteanu, Mount Sinai Hospital, Toronto, Ontario, CANADA; S. Thipphavong, L. White, Radiology, Princess Margaret Cancer Center, Torongo, Ontario, CANADA; A.A. Gupta, P. Bradbury, A. Razak, M. Blackstein, Medical Oncology, Princess Margaret Cancer Center, Toronto, Ontario, CANADA

Objective: Objective: DF are locally aggressive benign neoplasms that can occur sporadically, in association with familial adenomatous polyposis (FAP), as a result of injury or recent pregnancy. Optimal management of these benign tumors remains controversial. MTX/VBL is systemic therapy which is not associated with any long term sequelae. To date, reports of MTX/VBL have often included patients who have failed prior radiation therapy (RT) or other systemic therapy (ie. doxorubicin). We report our experience in management of patients with progressive DF with MTX/VBL, most of whom are treatment naive.Methods: Methods: Consecutive patients with DF treated between Jan 1994 and Dec 2015 were reviewed. Treatment: MTX 25 mg/m2 IV + VBL 25 mg/m2 IV d1,8,15 q28 d for a planned max duration of 24 cycles. Data including demographics, treatment details and toxicity were collected. A radiologist re-reviewed all available MRI scans to evaluate response by RECIST and T2 changes. PFS was estimated using KM.Results: Median age of 48 patients was 33 yrs (range 13-73). Thirty seven (77%) patients were treatment nave and 11 (23%) had residual/recurrent disease. Tumour location was as follows: 16 (33%) extremity, 13 (27%) abdominal wall, 4 (8%) head and neck, 6 (13%) chest wall/back, 7 (15%) mesenteric. Two patients (4%) had multifocal DF at two sites: abdominal wall and mesentery. Prior therapy in the 11 patients included: 6 (55%) surgery alone, 2 (18%) surgery and tamoxifen, 1(9%) surgery and RT, 1 (9%) tamoxifen alone and 1 (9%) tamoxifen and Doxorubicin. Median number of cycles of chemotherapy was 19 mos (range 1 to 27; Figure 1). Schedule modification occurred in 5 patients. The majority of patients (n=27, 56%) had 18 or more cycles of therapy; 9 completed 24 mo. Reasons for early therapy discontinuation before 24 months were: toxicity (n=2, 4%), response achieved (n=28, 58%%), patient preference (n=8, 17%), PD (n=1, 2%). Most severe toxicity was grade 1/2 fatigue, nausea or both in 9 (18%), 12 (25%) and 4 (8%) patients, respectively. Three (6%) patients had neutropenia (grade 1/2). At end of therapy, response was: 8 (17%) SD, 19 (40%) PR, 20 (41%) CR, and 1 (2%) PD for a clinical benefit rate of 98%. Median PFS was 95 mo (range 57.6 to 132.4), and 5-year PFS was 72%. Of the 10 patients who recurred, 5 had had prior therapy. 5-year PFS was 53% in those that completed less than 18 mo compared to 93% in those that completed more than 18 mo.Conclusion: MTX/VBL is very safe and very effective in the treatment of patients with DF and should be considered as first-line therapy. Duration of therapy of at least 18 months is likely required to ensure good outcome.

 

A RETROSPECTIVE COMPARISON OF PAZOPANIB WITH ESTABLISHED THERAPIES FOR DESMOID TUMORS IN PEDIATRIC, ADOLESCENT AND YOUNG ADULT (AYA) PATIENTS
Laura Agresta, R. Nagarajan, S. Szabo, B. Turpin, H. Kim, J. Sorger, J. Pressey, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

Objective: Desmoid tumors (DT) lack a reliably effective medical therapy. Surgical resection may be morbid and does not preclude recurrence. Radiation has potentially severe late effects, particularly detrimental in young patients. At our institution, we recently observed encouraging results with pazopanib therapy for DT compared with established therapies.Methods: Retrospective single-institution chart review comparing treatment outcomes in AYA and pediatric patients with DT treated with pazopanib to those treated with established therapies.Results: Six DT patients, 3-21 years with previously treated DT, received pazopanib; 33 DT patients received established therapies only. In both groups, the median age at diagnosis was 16 years, female patients comprised 50%, and most common DT site was extremity. In the pazopanib group, there were 4 patients with sporadic DTs, all with CTNNB1 mutations by next generation sequencing, and 2 FAP patients. In the comparison group, 5 sporadic DTs had CTNNB1 mutations and 1 had a somatic APC mutation. Established therapies showed few objective responses and most patients received multiple therapies as a result. Surgical resection had a 68% recurrence rate. One patient who received radiation developed a sarcoma in the radiation field. Of 8 patients who received vinblastine/methotrexate (VM), only 1 had a PR by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST), 5 had SD, 2 not evaluable. Toxicities included fever and neutropenia, peripheral neuropathy, nausea/vomiting. After VM, 5 of 8 required additional therapy. Of 7 patients who received sulindac/tamoxifen, none had objective improvement, 4 had SD, 1 had PD, 2 not evaluable. Five of 7 required additional therapy. All female patients developed ovarian cysts. In contrast, none of the patients progressed while on pazopanib. Best responses by RECIST were PR in 2 of 8 and SD in 6 of 8 tumors, and all extra-abdominal DTs demonstrated dramatically increased fibrosis on T2-weighted MR. A PR of 66% was observed in a patient who had failed multiple prior therapies. A mesenteric DT in a FAP patient also showed PR. Four of 6 patients reported substantial pain relief and improvement in function within 1 month. Pazopanib was discontinued in 1 patient after 18 months due to recurrent facial edema. All other toxicities responded to dose reduction and objective treatment effect was not sacrificed.Conclusion: In this series, pazopanib offered an effective treatment option for AYA patients with symptomatic DT.

 

FACTORS ASSOCIATED WITH DISEASE STABILIZATION IN DESMOID-TYPE FIBROMATOSES
Yong Sung Kim, M. Rosario, H. Kim, I. Han, Department of Orthopaedic Surgery, Seoul National University Hospital, Seoul, KOREA (THE REPUBLIC OF)

Objective: Spontaneous disease stabilization of desmoid-type fibromatosis (DF) has been demonstrated in many patients. Thus, watchful waiting approach without any front-line treatment is being offered to the patients who present with DF. To provide for the most suitable treatment for each patient, identification of factors predictive of disease stabilization is necessary. The purpose of this study was to assess the disease stabilization rate and identify predictive factors for disease stabilization.Methods: One hundred and forty-four patients with sporadic, extra-abdominal DF who were managed with front-line conservative treatment and followed for at least 2 years were reviewed. Tumors were radiologically diagnosed as stable when an unchanged or a continual decrease in tumor size by the longest diameter was successively recorded for at least 6 months with no renewed growth at final follow-up. The primary endpoint was tumor stabilization. Possible patient-, disease-, and treatment-related factors predictive of disease stabilization were examined. Kaplan-Meier method was used to estimate time to tumor stabilization, and the Log-rank test was utilized for univariate analysis. Multivariate analysis was performed using the Cox proportional hazards model.Results: One hundred sixteen (80.6%) out of 144 tumors were stable at final follow-up, with a mean time to stabilization of 17 months (range 0 to 153). Tumor stabilization rates at 1, 2, and 3 years were 59%, 72%, and 77%, respectively. On Kaplan-Meier analysis, patients <40 years (44.97.4 months vs. 7.31.5 months, p<0.001), with tumors ?5 cm (40.17.4 vs. 153.8 months, p=0.005), and with recurrence (49.28.2 vs. 9.12 months, p<0.001) were found to have significantly longer time to tumor stabilization. After multivariate Cox regression analysis, both recurrent presentation (RR=1.7, p=0.011) and younger age (RR=1.8, p=0.006) were the independent factors associated with disease stabilization. Analysis of recurrent disease showed 48 (67.6%) of the 71 recurrent tumors were stable at final follow-up, with a mean time to stabilization of 27 months (range 0 to 153). Stabilization rates for the recurrent tumors at 1, 2, and 3 years were 46%, 55%, and 62%, respectively.Conclusion: A front-line conservative treatment seems to be the optimal treatment for majority of patients who present with DF. Younger patients and those presenting with recurrence may require longer periods of initial observation with pain palliation as needed.

 

CLINIC AND MOLECULAR PROGNOSTIC FACTORS IN DESMOID TUMORS TREATED WITH UPFRONT SURGERY. A SPANISH GROUP FOR SARCOMA RESEARCH STUDY
Javier Martin-Broto, N. Hindi, Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, SPAIN; D.S. Moura, M. Lopez, Instituto Biomedicina Sevilla-IBIS, Sevilla, SPAIN; M. Da Conceicao, Hospital U Son Espases, Palma de Mallorca, SPAIN; D. Marcilla, Anatomia Patológica, Hospital U Virgen del Rocio, Sevilla, SPAIN; S. Bagué, Pathology, Hospital Sant Pau, Barcelona, SPAIN; R. Ramos, Pathology, Hospital U Son Espases, Palma de Mallorca, SPAIN; R. Alvarez, Medical Oncology, Hospital Gregorio Marañon, Madrid, SPAIN; C. Agra, Pathology, Hospital Gregorio Marañon, Madrid, SPAIN; A. Sala, Medical Oncology, Hospital de Basurto, Bilbao, SPAIN; A. Ugalde, Pathology, Hospital de Basurto, Bilbao, SPAIN; I. Sevilla, Medical Oncology, Hospital Virgen de la Victoria, Malaga, SPAIN; L. Vicioso, Pathology, Hospital Virgen de la Victoria , Malaga, SPAIN; A. López Pousa, Medical Oncology, Hospital Sant Pau, Barcelona, SPAIN

Objective: Desmoid tumor (DT) management has a wide spectrum of therapeutic options, and even when surgery is currently not recommended for most cases, the fact is that a relevant number of patients still undergo surgery as first option. Clinical behavior is difficult to predict at individual basis, even for those completely resected DT. In sporadic DT, the prognostic role of different missense mutations in CTNNB1 gene has been inconsistent among several publications. Our aim was to analyze the potential prognostic role of genotype in a series of primary DT treated with surgery.Methods: Patients were selected from GEIS registry, IRBs and ethic committees approved the protocol including molecular tests in paraffin embedded tumor samples. KaplanMeier estimations were used for time-to-event variables and the log-rank test was used to compare groups. Tumor tissue was processed with the QIAamp FFPE Tissue Kit (Qiagen, Valencia, CA), according to manufacturers instructions. Exonic primers were used to amplify a sequence within exon 3 of CTNN1B by PCR. Bidirectional sequencing with specific primers was performed in an AB 3500 genetic analyzer, using the BigDye Terminator v3.1 kit (Applied Biosystems).Results: A subset of 320 patients that underwent upfront surgery was selected. The median age was 37 y (12-89). Primary sites were: limbs 28%, trunk wall 43% and miscellany 29%. The median of size was 6.5 cm (1-27) and the median of Karnofsky index was 90% (50-100). There were 108 (34%) recurrences with a median follow-up of 60 months. Mutations in exon 3 of CTNNB1 gene were found in 142 (88%) out of 162 available blocks, 89 (63%) in 41A, 31 (22%) in 45F, 22 (15%) in 45P and 20 wild type (12%). Patients harboring 45F showed statistically worse SLR compared with the rest of genotypes: 25.8 m (16.4- 35,2) vs not reached, (p=0.035). Patients with DT in limbs had significant worse median of RFS: 38 m (3-73) than trunk wall (149) or miscellany (107), p= 0.001. Likewise, patients with DT ? 6.5 cm had significantly worse RFS: 59 m (17-101) vs not reached (p=0.003).Conclusion: Tumor site, tumor size and type of mutation of CTNNB1 gene has prognostic impact in DT treated with upfront surgery. Genotype 45F entails worse RFS and it justifies further molecular related research in this entity.

 

STABILIZATION OF β-CATENIN: A POTENTIAL THERAPEUTIC TARGET FOR DESMOID TUMORS?
Danielle Braggio, A. Zewdu, G. Lopez, K. Batte, L. Casadei, A. Strohecker, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA; F. Jin, M. Welliver, Radiation Oncology Department, The Ohio State University, Columbus, Ohio, USA; D. Koller, R. Pollock, Department of Surgery, The Ohio State University, Columbus, Ohio, USA; R. Soldi, Beta Cat Pharmaceuticals. INC, Houston, Texas, USA; D. Lev, Surgery B, Sheba Medical Center, Tel Aviv, ISRAEL

Objective: To investigate the antitumor effect of a novel agent targeting beta catenin stabilization, BC2059, in desmoid tumor (DT) models.Methods: A panel of DT cell strains was exposed to increasing concentrations of BC2059 in vitro and evaluated for cell proliferation and colony formation capacity. Antitumor effects were assessed in vitro by cell cycle, apoptosis, and migration and invasion analysis. Cells treated with BC2059 were analyzed the association of ?-catenin with TBL1 by immunoprecipitation (IP) analysis. To further understand the effects of BC2059 treatment on DTs we analyzed the expression of ?-catenin pathway components in DT cell strains treated with BC2059 using real time PCR and western blotting.Results: BC2059 markedly inhibited proliferation, capacity of colony formation, migration and invasion of mutated DT cells, but had no effect on wild-type DTs. Comparison of ?-catenin mutation between the original tumor and the associated cell strain was the primary method used to differentiate desmoid tumor cell from fibroblast. Therefore, cell strains lacking detectable ?-catenin mutation (wild-type) could be comprised of primarily fibroblasts cells and not tumor cells. This is one possible explanation for the lack of effect of BC2059 on DT wild-type cell strains. The decrease in cell viability on mutated DT cells caused by BC2059 was due to apoptosis. Treatment with BC2059 led to a reduction of ?-catenin associated TBL1 in all mutated DT cells, resulting in a reduction of nuclear ?-catenin. Consequently, levels of genes that are target of b-catenin (e.g MDK, AXIN2) were found to be downregulated after BC2059 treatment.Conclusion: Our findings suggest that BC2059 has significant antitumor activity against ?-catenin mutated DTs through stabilization of b-catenin that leads to downregulation of its target genes. Thus, BC2059 may comprise an alternative strategy for the treatment of desmoid tumor patients. * This work was made possible in part by funding of Beta Cat Pharmaceuticals through the Product Development Award CP130058 from the Cancer Prevention and Research Institute of Texas (CPRIT).

 

INVESTIGATION OF NOVEL EX VIVO TISSUE DRUG SCREENING TO PREDICT THERAPEUTIC RESPONSE IN DESMOID TUMORS
David Koller, D. Braggio, A. Zewdu, K. Batte, L. Casadei, G. Lopez, D. Lev, R. Pollock, The Ohio State University, Columbus, Ohio, USA

Objective: To investigate ex-vivo fresh tumor sensitivity as a predictor of tumor responsiveness in desmoid tumors and compare to standard of care.Methods: Fresh DT tissue have been thinly sliced and exposed to different drugs and combinations ex-vivo and evaluated for viability. The expression and activation of downstream markers were analyzed in DT ex-vivo tissue slice culture by western blot.Results: Ex-vivo tissue culture is used to test tissue responsiveness to chemotherapeutic options in DT fresh tissue. Confirmation of appropriate downstream protein inhibition through western blot shows appropriate targeting and modality of cell death.Conclusion: Ex-vivo tissue culture drug testing exhibits significant predictive effects on DT tissue with appropriate downstream effect in patient specific manner compared to in-vivo data. This data suggests that ex-vivo fresh tissue drug testing may be an appropriate drug selection technique in addition to pathology and genomic data in predicting adjuvant and salvage therapy after surgical treatment. This data suggest that quick and easy personalized treatments can be tested and selected through ex-vivo culture and testing to allow optimal treatment selection. Furthermore, our results suggest that along with previous therapies, novel treatment can be tested as well.

 

TUMOR REDUCTION AND SYMPTOM RELIEF AFTER ELECTROCHEMOTHERAPY IN A PATIENT WITH AGGRESSIVE FIBROMATOSIS
Joanna Vitfell-Rasmussen, R.M. Sandvik, K. Gehl, A. Krarup-Hansen, Oncology, Herlev University Hospital, Herlev, DENMARK; K. Dahlstrøm, Plastic Surgery, Herlev University Hospital, Herlev, DENMARK; G. Al-Farra, Radiology, Herlev University Hospital, Herlev, DENMARK

Objective: Aggressive fibromatosis also known as desmoid tumors constitute 3% of soft tissue tumors. It is a monoclonal (myo-) fibroblastic proliferation derived from mesenchymal progenitor cells. These tumors commonly develop in the fibrous (connective) tissue of the body that forms tendons and ligaments, usually in the arms, legs or midsection but also in the head and neck area. Electrochemotherapy (the use of brief electric pulses to enhance uptake of chemotherapy) is increasingly being used to treat cutaneous and subcutaneous tumors of different histologies, however the use for aggressive fibromatosis has not previously been reported in humans.Methods: This case report describes a 63-year old woman with subcutaneous aggressive fibromatosis in the neck region of which the main symptom was severe pain, despite medication. At diagnosis, surgery was not feasible and radiotherapy not performed due to the diagnosis of familial adenomatous polyposis. Previous treatments included NSAID, endocrine therapy and sorafenib, which the patient had to stop due to severe side effects. After thorough consideration and discussion of various treatment options, the patient was referred for consideration of electrochemotherapy. She was informed that electrochemotherapy was considered experimental treatment in her particular case and consented to treatment. The patient was treated twice with electrochemotherapy with a 5 month interval, with 26.000 international units (IU) of bleomycin (15.000 IU/m2) and 64 pulse sequences of each eight pulses were administered using a square wave pulse generator (Cliniporator, IGEA, Carpi, Italy), and linear array electrodes. See figure 1.Results: At one year follow-up substantial tumor reduction (7.1 x 2.2 cm to 2.9 x 1.7 cm) was observed both clinically and on MRI, and the patient went from reporting severe pain, NRS (numeric rating scale) score 7 to mild pain, NRS score 2 without pain medication. See figure 2. Side effects to the treatment with electrochemotherapy were considered mild and consisted of pain, inflammation and hyperpigmentation of the treated skin area.Conclusion: This case study opens up the possibility of treating aggressive fibromatosis close to the skin with electrochemotherapy, and warrants phase II studies to investigate clinical outcomes in greater detail.

 

IONIZING RADIATION ENHANCES THE SENSITIVITY OF DESMOID TUMOR CTNNB1 S45F MUTANT TO SORAFENIB
Feng Jin, S. Savinoff, M. Welliver, Radiation Oncology, The Ohio State University, Columbus, Ohio, USA; D. Braggio, D. Lev, R. Pollock, The Comprehensive Cancer Center, Columbus, Ohio, USA

Objective: To test whether sorafenib or radiotherapy (RT) are effective agents for DT with S45F mutation, and whether the combination of RT with Sorafenib is additive or synergistic treatment.Methods: We treated the desmoid cell strains isolated from patient tumors with various doses of sorafenib, radiation or both and examined the cell survival with soft agar assays.Results: Both the wild type and S45F mutant DT cell lines responded well to radiation in a dose-dependent manner. Sorafenib significantly inhibited capacity of colony formation and cell proliferation of mutant DT cells, but had no notable effect on the wide type cells. The CTNNB1 S45F mutant cells also showed the sensitivity to Sorafenib in a dose-dependent manner. Combination treatment of Sorafenib and radiation resulted in additive effects on cellular anchorage-independent growth.Conclusion: A combination treatment of Sorafenib and radiation could be good strategy for the treatment of desmoid tumor patients and clinical trials should be explored.

 

MRI FEATURES PREDICTIVE OF RESPONSE TO METHOTREXATE AND VINORELBINE IN DESMOID FIBROMATOSIS
Sally Burtenshaw, A. Olteanu, R. Gladdy, General Surgery, Mount Sinai Hospital, Toronto, Ontario, CANADA; A.A. Gupta, Medical Oncology, Princess Margaret Cancer Centre, Canada, Ontario, CANADA; S. Thipphavong, Medical Imaging, Princess Margaret Cancer Centre, Toronto, Ontario, CANADA

Objective: Desmoid fibromatosis (DF) is a mesenchymal tumor that is locally aggressive and historically treated with surgical resection, with high recurrence rates. Systemic treatment of progressive DF can be associated with improved progression-free rates however the use of medical therapy remains controversial. Also, treatment response as defined by RECIST 1.1 by measuring maximum tumor dimension (Dmax) may not accurately evaluate response to medical treatment in desmoid patients. We sought to assess if imaging parameters such as approximate tumor volume (Vtumor) and MRI features, specifically T2 signal were more predictive of response to medical therapy than Dmax.Methods: A retrospective chart review between 1997 and 2015 identified 22 patients with biopsy proven DF treated with Methotrexate and Vinorelbine and followed with MRI throughout treatment. Dmax, Vtumor and quantitative T2 hyperintensity using interquartile range scoring on MRI were compared pre, mid (between 3-9 months) and post-treatment. On T2-weighted or T2-weighted fat-saturated MRI images, tumors were ranked as containing: 0-25%, 25-50%, 50-75% or 75-100% of internal high T2-signal intensity. Treatment response was defined as: partial response (PR) if the size or T2 quartile score decreased, stable disease (SD) if there was no change in size or T2 quartile, progression of disease (PD) if there was an increase in size or increase in T2 quartile, and complete response (CR) if size decreased and/or the entire lesion was hypointense on T2-weighted images.Results: Mean age was 31 yrs with 17 females and 5 males. Patients presented with primary (n=18) or recurrent/residual (n=4) with DF of the extremity (n=9), abdominal wall (n=7), head and neck (n=3), chest wall/back (n=2) or mesentery (n=1). At end of treatment (median 20 mos (range 9-27)), Dmax mean decreased by -30% and Vtumor decreased by -76% overall. On T2 weighted imaging, CR was observed in 13 and PR in 5 patients. Mid treatment, 2 had PD and 7 had SD as per Dmax and Vtumor with T2 change indicative of PR in all cases. Both patients with PD continued therapy and had CR at end of treatment. Four patients progressed post treatment, median PFS was 31 months (95% CI: 14.9-137) and all had complete response (CR) on T2 imaging treatment end.Conclusion: Evaluation of treatment response for DF utilizing an estimated volume of tumor and monitoring the degree of T2-weighted signal intensity change within the tumor may be better predictors of response to medical therapy than maximum tumor dimension. Findings from this study warrant prospective multi-institutional validation.

 

DIFFERENTIATION OF ENDOMETRIOMAS AND DESMOIDS IN THE ANTERIOR ABDOMINAL WALL IN FEMALES OF REPRODUCTIVE AGE
Nolan Walker, P. Lykoudis, P. Dileo, M. Novelli, A. Shankar, J.T. Lordan, Sarcoma Surgery, Royal Free London and University College London, London, UNITED KINGDOM

Objective: Desmoids and endometriomas are rare, predominantly present in females of reproductive age. Endometriomas maybe be left in situ and often atrophy during pregnancy and post-menopause, unlike desmoids. Endometriomas rarely recur after excision, whereas desmoids frequently recur and so often require extensive resection. Differentiation prior to management is essential. This study was designed to determine distinguishing clinical and radiological features between desmoids and endometriomas of the anterior abdominal wall.Methods: This was a retrospective comparative analysis over eleven years (January 2006 to December 2016) in a high volume sarcoma centre. Patients with endometriomas (n=27) and desmoids (n=110) were identified. The inclusion criteria were; female, reproductive age, anterior abdominal wall, inferior to the umbilicus. Patients were excluded if there were inadequate records of radiological or clinical features. Endometriomas (n=23) and desmoids (n=19) were compared. Radiological features included; size, location (subcutaneous v intramuscular), magnetic resonance imaging T1 and T2 signal, restriction diffusion imaging, imaging characteristics (heterogenous/homogenous, internal fluid locules), and border definition. Continuous data were reported as means with p values from Paired T tests, and categorical data reported as percentages and p values from McNemar or Fishers exact tests.Results: Clinically, 50% of patients with endometriomas reported cyclical symptoms, compared with zero patients with desmoids (p=0.007). The mean age for patients with desmoids and endometriomas was 34 years and 37 years respectively (p=0.71). Mean tumour size of desmoids and endometriomas was 6.8cm and 3.1cm respectively (p<0.0001). 70% of endometriomas and 58% of desmoids were heterogenous (p=0.32). Desmoids had a greater incidence of internal fluid locules (93% v 50%, p=0.03). There was no difference in exhibition of bright T2 areas (75% v 53%, p=0.19) between desmoids and endometriomas respectively. There was a greater number of desmoids with a low T1 signal (88% v 53%, p=0.04). All desmoids and endometriomas exhibited restricted diffusion and enhancement.Conclusion: Endometriomas and desmoids occur infrequently and can be challenging to differentiate. However, endometriomas may be associated with smaller size and cyclical pain, while desmoids may have a greater incidence of low T1 signal. We recommend obtaining histological or cytological diagnosis prior to management

 

HIGH THROUGHPUT GENOME STUDY TO IDENTIFY PREDICTORS OF AGGRESSIVENESS IN PATIENTS WITH SPORADIC DESMOID TUMOR WHO UNDERGO A WAIT AND SEE APPROACH
Chiara Colombo, M. Fiore, A. Gronchi, Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ITALY; M. Urbini, A. Astolfi, V. Indio, M. Pantaleo, “Giorgio Prodi” Cancer Research Center, Bologna, ITALY; P. Collini, A. Belfiore, N. Paielli, F. Perrone, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ITALY

Objective: Wait and see approach for desmoid-type fibromatosis (DF) patients has become part of the routine treatment strategy. Two parallel European prospective studies have been conducted to validate this approach. However, predictive factors to select the risk of progressive disease in the individual patient are still lacking. A translational project was run in order to identify genomic signatures associated to specific behaviors in patients enrolled within the Italian prospective observational study.Methods: DF fresh frozen samples from enrolled patients who have been biopsied at our Institution were collected for translational studies. Whole exome sequencing was performed on DNA extracted from 12 fresh frozen biopsies using Nextseq500 (Illumina, CA) sequencer. Deep sequencing of CTNNB1, APC and LAMTOR2 was performed on additional 12 FFPE cases of WT DF using Truseq custom amplicon low input kit (illumina) for library preparation and sequenced on MiSeq instrument (illumina).Results: Twelve fresh frozen biopsies were analyzed through exome sequencing. Using Sanger sequencing 10 mutated DF (8 T41A and 2 S45F) and 2 WT were identified. In WT cases, two genes were found to be mutated: APC in one case (p.D1696N and p.D1670H) and LAMTOR2 (p.V92M) in the other. Globally, DF exhibited low somatic sequence mutation rate (mean 0.36 mutations per megabase), and in the CTNNB1-mutated group no other recurrent mutational event was identified. Overall, in this group, only 2/12 patients (17%) were shifted from an observational approach to a specific treatment for progressive disease. In order to enlarge the study on WT DF subtype and identified new potential mutations, high deep sequencing of CTNNB1, APC and LAMTOR2 was conducted on a retrospective series of 12 additional WT DF. No other mutation of LAMTOR2 was detected. APC mutation was detected in one case, while low-frequencies CTNNB1 mutations were found in 6 samples (50%) (mean of 16% reads). However, 5 cases (42%) remained WT for CTNNB1 or APC mutations. Further analyses are ongoing in this subgroup to identify other potential molecular events determining tumorigenesis.Conclusion: DF is characterized by a low load of mutational events, which do not seem to be associated to the clinical course of the disease. A minority of DF is wild type for either CTNNB1, APC or any other gene involved in the WNT pathway. The clinical and molecular meanings of these findings need further investigation.

 

TREATMENT AND PROGNOSIS OF DESMOID TUMORS: A SINGLE INSTITUTIONAL EXPERIENCE OF 189 PATIENTS
Jaekyung Cheon, Ulsan University Hospital, Ulsan, KOREA (THE REPUBLIC OF); J. Kim, J. Ahn, Asan Medical Center, Seoul, KOREA (THE REPUBLIC OF)

Objective: Desmoid tumors (DTs) are locally infiltrating soft-tissue neoplasm that grow slowly and arise from musculoaponeurotic stromal elements. DTs usually occurs sporadically but 5~10% of them are associated with familial adenomatous polyposis (FAP). Because of rarity of DTs, there are relatively few data on its epidemiology and long term outcomes.Methods: We analyzed the data of 189 patients who were diagnosed as DT from October 1992 to August 2015 using Asan Medical Center Sarcoma Registry. Clinicopathologic features and treatment related data were analyzed to identify predictive factor for recurrence.Results: A total of 189 patients were included for the analysis. The median age of patients was 39 years old (range, 0-96) and 108 patients (57.1%) were female. Familial history of FAP was present in 13 patients (6.8%). The most common primary tumor site was abdominal wall (38.1%), followed by the abdominal cavity (34.9%), retroperitoneum (15.8%) and extremities (5.3%). The median tumor size was 5.0 cm (range, 0.5-25.0 cm). Among 177 patients who underwent treatments, 165 patients (93.2%) received surgery, 11 patients received systemic therapy and one patient underwent radiotherapy for the 1st line treatment. Majority of patients who underwent surgery, had R0, R1 surgical margin (46.1%, 44.8%, respectively). With a median follow-up of 29.7 months, 15 patients (7.9%) showed recurrence after surgery within a median time interval of 15.5 months. In univariate analysis, sex, age, tumor size, tumor location, and surgical margin had no significant impact on recurrence. Out of 15 patients with recurrence, 3 patients had familial history of FAP. When patients were divided into 3 groups according to primary site: abdominal wall, intraabdominal, extraabdominal group, the number of patients with recurrent disease were 5, 4, and 6 (7.0%, 6.0% and 11.8% respectively). Of the 6 recurrent cases in which the primary site was located in the extraabdominal region, 3 patients showed 2nd recurrence, and they underwent resection. Two of 3 patients with 2nd recurrence had 3rd recurrence.Conclusion: Recurrence remains a problem following surgery of DTs. In the patients with extraabdominal site DTs, the recurrence rate tends to be higher. These patients may recur again even after curative surgical resection, therefore careful follow up is required.

Miscellaneous

An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG)
Abstract: Desmoid-type fibromatosis (DF) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals’ AND patients’ expertise following a round table meeting bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patients and patient advocates from Sarcoma Patients EuroNet (SPAEN). In this paper, we focus on new findings regarding the prognostic value of mutational analysis in DF patients and new systemic treatment options.  

Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF- 03084014, an Oral Gamma Secretase Inhibitor, Victor Villalobos, MD, PhD, University of Colorado-Denver

“Biology & Treatment of Aggressive Fibromatosis or Desmoid Tumor”, Keith Skubitz, MD   Childhood Soft Tissue Sarcoma Treatment (PDQ®): Health Professional Version
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood soft tissue sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).  

Abdominal Wall Reconstruction
Abdominal wall reconstruction has become a frequently used term to describe hernia repairs that try to recreate the abdominal wall and restore function and structure. Although there has been no true definition of a functional abdominal wall, many surgeons believe this involves the closure of the fascia at the midline often with reinforcement using mesh prosthetics. The integrity of the abdominal wall is vital as it serves to protect the internal organs, supports the spine and helps maintain an upright posture. Several tumors can occur on the abdominal wall, and the most common are desmoid tumors. These lesions even though histologically benign, often are very locally invasive. Treatment of desmoids often requires full thickness abdominal wall excision. Despite this, local recurrence rates are nearly 40% to 50%. Most of these recurrences occur within the first 24 months after surgery. In some cases, adjuvant radiation therapy is recommended especially when the margins are not clear. Management of malignant lesions of the abdominal wall requires aggressive resection of the subcutaneous tissues and skin, as well as any involved muscle. Sarcomas are the most common tumors of the abdominal wall and require aggressive resection, followed by radiotherapy. There may also be some intraabdominal wall tumors either via hematogenous or contiguous spread that require resection. Reconstruction of the abdominal wall in these cases is usually directed by the extent of resection and the possibility of further surgical intervention.

2016 ASCO Annual Meeting

Abstracts

  • Geraldine Helen O’Sullivan Coyne, Shivaani Kummar, Khanh Tu Do, Peter L. Choyke, Baris Turkbey, Eric Polley, Yvonne Horneffer, Lamin Juwara, Rasa J Vilimas, Robert S. Meehan, Lee J. Helman, James H. Doroshow, Alice P. Chen; Early Clinical Trials Development Program, DCTD, National Cancer Institute at the National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Dana-Farber Cancer Center/Brigham and Women’s Hospital, Boston, MA; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD; Mayo Clinic, Rochester, MN; Leidos BioMedical Research, Inc, Bethesda, MD; Early Clinical Trials Development Program, DCTD, NCI, Bethesda, MD; Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD; Early Clinical Trials Development Program, National Cancer Institute at the National Institutes of Health, Bethesda, MD
    Activity of PF-03084014 in adults with desmoid tumors/aggressive fibromatosis.

 

 

  • Olivier Mir, Chahinez Rahal, Françoise Rimareix, Julien Adam, Philippe Terrier, Julien Domont, Sarah Dumont, Arslane Skander Rahal, Andrea Cavalcanti, Isabelle Sourrouille, Nicolas Leymarie, Charles Court, Gilles Missenard, Leila Haddag-Miliani, Charles Honoré, Axel Le Cesne; Gustave Roussy Cancer Campus, Department of Medical Oncology, Villejuif, France; Gustave Roussy Cancer Campus, Villejuif, France; Department of Biopathology, Gustave Roussy Cancer Center, Villejuif, France
    Efficacy of oral vinorelbine in advanced/progressive desmoid tumours: An updated retrospective study in 50 patients.

 

 

  • Rodrigo Ramella Munhoz, Robert A Lefkowitz, Deborah Kuk, Mark Andrew Dickson, Sandra P. D’Angelo, Mary Louise Keohan, Ping Chi, Aimee Marie Crago, Robert G. Maki, Gary K. Schwartz, Li-Xuan Qin, William D. Tap, Mrinal M. Gounder; Hospital Sírio Libanês, São Paulo, Brazil; Memorial Sloan Kettering Cancer Center, New York, NY; Icahn School of Medicine at Mount Sinai, New York, NY; Columbia University Medical Center – New York Presbyterian Hospital, New York, NY
    Efficacy of sorafenib in patients with desmoid-type fibromatosis.

 

 

Posters

  • Rodrigo Ramella Munhoz, Robert A Lefkowitz, Deborah Kuk, Mark Andrew Dickson, Sandra P. D’Angelo, Mary Louise Keohan, Ping Chi, Aimee Marie Crago, Robert G. Maki, Gary K. Schwartz, Li-Xuan Qin, William D. Tap, Mrinal M. Gounder; Hospital Sírio Libanês, São Paulo, Brazil; Memorial Sloan Kettering Cancer Center, New York, NY; Icahn School of Medicine at Mount Sinai, New York, NY; Columbia University Medical Center – New York Presbyterian Hospital, New York, NY
    Efficacy of sorafenib in patients with desmoid-type fibromatosis.”

 

  • Geraldine Helen O’Sullivan Coyne, Shivaani Kummar, Khanh Tu Do, Peter L. Choyke, Baris Turkbey, Eric Polley, Yvonne Horneffer, Lamin Juwara, Rasa J Vilimas, Robert S. Meehan, Lee J. Helman, James H. Doroshow, Alice P. Chen; Early Clinical Trials Development Program, DCTD, National Cancer Institute at the National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Dana-Farber Cancer Center/Brigham and Women’s Hospital, Boston, MA; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD; Mayo Clinic, Rochester, MN; Leidos BioMedical Research, Inc, Bethesda, MD; Early Clinical Trials Development Program, DCTD, NCI, Bethesda, MD; Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD; Early Clinical Trials Development Program, National Cancer Institute at the National Institutes of Health, Bethesda, MD
    Activity of PF-03084014 in adults with desmoid tumors/aggressive fibromatosis.

 

2016 DTRF Research Workshop Abstracts & Presentations

  • Benjamin Alman, MD, Department Chair, Orthopedic Surgery, Duke University, 
    “Introduction and Report on Collaboration for a Cure project.”  

 

  • Kris Vleminckx, PhD, Professor of Developmental Biology, Ghent University
    “Identifying targets for therapy in a novel genetic Xenopus model for desmoid tumor formation.”  Abstract

 

  • Stephen Horrigan, PhD, Chief Scientific Officer, BetaCat Pharmaceuticals
    “Tegatrabetan (BC-2059) – A new approach to targeting beta catenin and Wnt activation.”  Abstract

 

  • Danielle Braggio, PhD, Post-Doctoral Researcher, Ohio State University
    “Initial studies of Tegatrabetan (BC-2059) in desmoid tumor cell strains.”  Abstract

 

  • Mrinal Gounder, MD, Assistant Professor and Medical Oncologist, Memorial Sloan Kettering Cancer Center,
    “Development of PRO tool in desmoid tumors.”  

 

  • Steven Attia, DO, Assistant Professor of Oncology, Mayo Clinic
    “A model for international, multi-institutional, multi-disciplinary sarcoma videoconferencing.”  Abstract

 

  • Nicholas Penel, MD, PhD, Medical Oncology, Centre Oscar Lambret
    “The French Patient Registry Project.”  Abstract

 

  • Danique van Broekhoven, MD, Surgical Oncology, Erasmus MC
    “Outcome of non-surgical management of extra-abdominal and abdominal desmoid-type fibromatosis: a population based study.”  Abstract

 

  • Matt van de Rijn, MD, PhD, Professor, Department of Pathology, Stanford University Medical Center,
    “Gene expression profiling of desmoid tumors.”  

 

  • Danielle Braggio, PhD, Post-Doctoral Researcher, Ohio State University
    “Investigation of antitumor effects of sorafenib on desmoid tumors.”  Abstract

 

  • Lara Sullivan, MD, MBA, Vice President, Pfizer CURES, Pfizer, Inc.,
    “Update on clinical trials on Pfizer compound/ a potential new treatment.”  

 

  • Peter Hohenberger, MD, Mannheim University Medical Center
    “An analysis of incidence and significance of trauma prior to desmoid tumor formation.”  Abstract

 

  • Nancy Cho, MD, Assistant Professor of Surgery, Harvard Medical School
    “Targeting hyaluronic acid in desmoid tumors.”   Abstract

 

  • Chiara Colombo, MD, Surgical Oncology, Instituto Tumori di Milano
    “Whole Exome Sequencing in patients under Wait & See (W&S): a preliminary analysis.”  Abstract

 

  • Daniela Segat, PhD, Senior Researcher, ”Mauro Baschirotto” Institute for Rare Diseases – B.I.R.D. Foundation,
    “In vitro studies of the microenvironmental factors responsible of the proliferation and aggressiveness of desmoid tumor cells.”  Abstract  |  Presentation

2016 CTOS Meeting

Abstract

 

 

Paper

 

Presentation

 

 

2016 DTRF Patient Meeting Abstracts & Presentations

  • Raffi Avedian, MD, The Stanford University Medical Center.
    “Magnetic resonance guided high intensity focused ultrasound: a novel noninvasive technique to treat soft tissue tumors of the extremity.”  Abstract

 

  • Geraldine O’Sullivan Coyne, MD, PhD, NCI- NIH.
    “NCI’s Phase II trial of PF-03084014 in adults with desmoid tumors/aggressive fibromatosis.”  Abstract

 

  • Benjamin Alman, MD, Duke University.
    “Collaboration for a Cure: what we’ve learned so far.”  Abstract

 

  • Kris Vleminckx, PhD, Ghent University.
    “Fishing for New Therapeutic Targets in the Frog Pond.”

 

  • Raphael E. Pollock, MD, PhD, Ohio State University Comprehensive Cancer Center. 
    “Understanding the S45F and T41A mutations in desmoid tumors. What is their significance?”  Abstract  |  Presentation

 

  • Kelly Mercier, PhD, RTI International.
    “Natural History Study and DTRF Patient Registry.”  Abstract  |  Presentation

 

  • Sunil Sharma, MD, University of Utah School of Medicine, Expert in Oncology Drug Development.
    “Targeting beta-catenin as a treatment for desmoid tumors.”  Abstract  |  Presentation

 

  • Ian Bier, ND, PhD, LAc, FABNO, Human Nature Natural Health.
    “Naturopathic Oncology: What is it, and how can it help?”  Presentation

 

Miscellaneous

  • Dr. Bernd Kasper of Mannheim University Medical Center
    Brief video followup on “Clinical and translational research results of a phase II study evaluating imatinib to induce progression arrest in RECIST progressive desmoid tumors- A study of the German Interdisciplinary Sarcoma Group (GISG- 01)”

2015 CTOS Meeting

  • Jacob Bickels, MD, Orthopaedic Oncology, Sourasky Medical Center, Israel
    Poster: “Aminolevulinic acid photoablation of fibrotic soft-tissue tumors: preliminary report of 24 patients.”

 

  • Chiara Colombo, MD, Surgical Oncology, Fondazione IRCCS Istituto Tumori di Milano
    Poster: “Gene expression analysis identifies a potential role of immune system in CTNNB1 mutated desmoid tumors.”

 

  • Amanda Kirane, MD, Surgery, Memorial Sloan Kettering Cancer Center
    Poster: “Progression of desmoid-type fibromatosis during active observation is associated with tumor size.”
    Poster: “Molecular characterization of desmoid tumors.”

2015 DTRF Patient Meeting Presentations

  • Benjamin Alman, MD, Duke University
    “Collaboration for a cure: What we’ve learned so far.”  Presentation

 

  • Aimee Crago, MD, PhD, Memorial Sloan Kettering Cancer Center
    “Personalizing management of desmoid tumors.”  Presentation

 

  • Kishore Iyer, FRCS, FACS, Mount Sinai Hospital
    “Challenging Conventional Limits of Inoperability in Abdominal Desmoids and Sarcomas.”  Presentation

 

  • Robert Lefkowitz, MD, Memorial Sloan Kettering Cancer Center
    “MR Imaging of Desmoid Tumors.”  Presentation

 

  • Bernd Kasper, MD, PhD, Mannheim University Medical Center
    “The European Experience”  Presentation

 

  • Jean Paty, PhD, Principle, Advisory Services, Quintiles
    “DTRF’s PRO Development Study.”  Presentation

 

2015 DTRF Research Workshop Abstracts & Presentations

  • Mushriq Al-Jazrawe, University of Toronto
    “Single cell-derived clonal analysis of desmoid tumors.”  Abstract  |  Presentation

 

  • Radhika Atit, PhD, Case Western University
    “Sustained β-catenin activation in dermal fibroblasts promotes fibrosis by regulating cell proliferation and extracellular matrix protein-coding genes.”  Presentation

 

  • Benjamin Alman, MD, Duke University
    “From the bedside to the bench and the back again.”  Presentation

 

  • Danielle Braggio, PhD, Ohio State University
    “Reactivation of apoptosis as a potential therapeutic target for desmoid tumors with CTNNB1 S45F mutation.”  Abstract  |  Presentation
    “Targeting the notch pathway: a potential therapeutic approach for desmoid tumors.”  Abstract
    “Desmoid Tumors Harboring S45F B-catenin Mutation are Highly Resistant to Apoptosis.”  Presentation

 

  • Alice Chen, MD, National Institutes of Health/ National Cancer Institute
    “A Phase II trial of PF-03084014 in adults with Desmoid tumors/Aggressive Fibromatosis.”  Abstract  |  Presentation

 

  • Meredith Chuk, MD, Food and Drug Administration
    “FDA Draft Guidance- Rare Diseases: Common Issues in Drug Development.”  Presentation

 

  • Aimee Crago, MD, PhD, Memorial Sloan Kettering Cancer Center
    “Oncogenic effects of activated beta-catenin in desmoid fibromatosis.”  Abstract
    “Whole Exome Sequencing and Integrated Genomic Analysis of ‘Wild-Type’ Desmoids Identifies Potential Drivers of Tumor Initiation.”  Abstract

 

  • Alessandro Datti, PhD, SMART Laboratory for High Throughput Screening Programs
    “Introduction to drug repositioning towards novel therapeutics for desmoid tumors.”  Presentation

 

  • Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center
    “Notch inhibition in desmoids: Sure it works in practice, but does it work in theory?”  Article

 

  • Katherine Hartley, MD, Vanderbilt University
    “Image-guided cryoablation for desmoid tumors: successes, challenges and lessons learned.”  Poster
    “16α-[18F]-fluoro-17ß-estradiol (18F-FES) PET/CT Imaging of Estrogen Receptor Activity in Desmoid Tumors.”  Poster

 

  • Bernd Kasper, MD, PhD, Mannheim University Medical Center
    “Clinical and translational research results of a phase II study evaluating imatinib to induce progression arrest in RECIST progressive desmoid tumors- A study of the German Interdisciplinary Sarcoma Group (GISG- 01).”  Presentation

 

  • Kelly Mercier, PhD, RTI International
    “Metabolomics: Towards a Better Understanding of Desmoid Tumors.”  Abstract  |  Presentation

 

  • Yoshihiro Nishida, MD, PhD, Nagoya University
    “Planned simple resection for selected patients with extra-peritoneal desmoid tumors.”  Abstract  |  Presentation

 

  • Raphael Pollock, MD, PhD, Ohio State University
    “Targeting the notch pathway: A potential therapeutic approach to desmoid tumors.”  Article

 

  • Ty Subhawong, University of Miami Miller School of Medicine
    “MRI Features of Response in Systemic Therapy for Aggressive Fibromatosis.”  Presentation

 

2013 SPAEN Conference

 

 

 

 

Miscellaneous

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