The Connective Tissue Oncology Society

#35006 DESMOID TUMOURS: TO OPERATE OR NOT TO OPERATE
Rafi q H Abed, Adesegun Abudu, Simon Carter, Rob Grimer, Roger Tillman, Lee Jeys
The Royal Orthopaedic Hospital, Birmingham, United Kingdom
Objectives: The best local treatment for desmoid tumours remains unclear. We reviewed our experience of treatment of desmoid fibromatosis and report on observation only modality in the treatment of desmoids tumours.
Methods: Retrospective review of all patients treated under a multidisciplinary team was performed. The clinical data were studied. Information regarding recurrence was obtained including timing, progression, treatment, timing of treatment and any subsequent recurrence.
Results: 160 patients were studied at mean follow up of 49 months and mean age 36 years. Male to female ratio was 1:1. 114 patients presented with primary disease and 46 presented with recurrent disease. Mean tumour size was 8.6cm (2-25). 147 patients had surgical treatment with very few having adjuvant radiotherapy. Overall recurrence rate was 41%. Recurrence for patients with primary and recurrent presentations was 30% and 66% respectively. Recurrence was more common in females. Margins of resection had no infl uence on recurrence. 33 patients had observation only treatment either at presentation or after recurrence. 22 patients (67%) remained in stable disease, 3 patients in active progressive disease and 8 patients had further surgery due to progression or pain.
Conclusions: Fibromatosis is a benign condition with aggressive behaviour and high recurrence rate. Our series experience is that recurrence is common after surgery even with radiotherapy. Surgical margins did not infl uence local recurrence. Observation alone appears to be the best policy for those with painless desmod tumours.

#34885 THE DESMOID TUMOR PROTEOME; IDENTIFYING MOLECULAR MARKERS USING A CLINICALLY ANNOTATED TISSUE MICROARRAY (see Details)
Shohrae Hajibashi, Wei-Lien Wang, Alexander J.F. Lazar, Daniel Tuvin, Carla L. Warneke, Dolores Lopez-Terrada, Raphael E. Pollock, Dina Lev
The University of Texas MD Anderson Cancer Center, Houston, TX, United States
Objectives: To establish a clinically annotated tissue microarray (TMA) useful for correlating protein marker expression with desmoid outcomes.
Methods: A TMA that included 0.6 mm punch samples (2/case) of desmoid (n=195) and scar (n=18) was formatted into 3 standard blocks. Demographic, therapeutic, tumor, and clinical outcome data were retrieved from medical records and our soft tissue tumor database, then tabulated for correlative analyses. IHC assays were performed to identify beta-catenin, cyclin D, p53, ER-beta, c-Kit, EGFR, PDGFRs and PDGFs expression as scored by a soft tissue pathologist. Associations between possible predictors of time from primary surgery to recurrence were statistically evaluated.
Results: Nuclear beta-catenin was observed in 98% of desmoids; compared to scars, desmoids had greater percentage reactivity and intensity in nuclear and cytoplasmic compartments (p<0.0001). In primary desmoids (n=81), less intense beta-catenin nuclear staining with increased recurrence (p=0.0406). Cyclin D1 expression was observed in 34% of primary desmoids; increased nuclear cyclin D reactivity cases had higher levels of nuclear beta-catenin and lower recurrence (p<0.01). Strong nuclear p53 staining was observed in 17% of cases and associated with increased recurrence (p=0.0290). EGFR, c-KIT, ER-beta, PDGFR alpha and beta, and PDGF A and B reactivity did not correlate with desmoid outcome.
Conclusions: These studies demonstrate that higher nuclear beta-catenin intensity and increased nuclear cyclin D reactivity associate with less aggressive desmoid behaviors, whereas nuclear p53 expression associates with increased recurrence, observations warranting further investigation. Desmoid TMAs are useful for identifying novel prognostic factors that are also potentially exploitable as therapeutic targets.

#35119 MESENCHYMAL PROGENITOR CELLS ARE INVOLVED IN THE FORMATION OF AGGRESSIVE FIBROMATOSIS (DESMOID TUMOR)
Colleen Wu, Benjamin A Alman
Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
Objectives: Aggressive fi bromatosis (AF), also called desmoid tumor is a locally invasive soft tissue lesion associated with activation of beta-catenin mediated signaling. Although the location, cellular morphology and histological profi le of these tumors suggest that they may be of mesenchymal origins; the cell of origin has yet to be defi nitively elucidated.
Methods: Genetically engineered mice predisposed to developing AF, the Apc1638N mouse, were used in this study. The number of colony forming units fi broblastic (CFU-F, whose numbers are surrogates for mesenchymal progenitor cells) was compared with the number of AF tumors. The mice were crossed with Sca1-/- mice, which are defi cient in mesenchymal progenitors to determine the effect on tumor number. Bone marrow stromal cells from Apc 1638N mice or wild type littermates were injected into immuno-defi cient, NOD/SCID mice to determine if they would form tumors.
Results: The number of AF tumors in individual mice positively correlated with the numbers of CFU-F in their bone marrow, Apc 1638N mice lacking Sca-1 demonstrated substantially reduced numbers of AF tumors compared to littermate control mice expressing wild type Sca-1. Bone marrow stromal cells from Apc 1638N mice induced aberrant cellular growth when injected subcutaneously into NOD/SCID mice. In contrast, bone marrow stromal cells from wild type littermates did not result in tumor formation.
Conclusions: Taken together this suggests that AF derives from mesenchymal progenitor cells. Identifi cation of the cell of origin in this neoplasm, may allow for the development of targeted therapies that will improve the outcome for patients with AF.

#34904 MULTIMODALITY TREATMENT OF MESENTERIC DESMOID TUMORS
Monica M Bertagnolli, Jeffrey A Morgan, Christopher DM Fletcher, Chandrajit P Raut, Palma Dileo, Ritu R Gill, George D Demetri, Suzanne George
Dana Farber Cancer Institute, Boston, MA, United States; Brigham and Womans Hospital, Boston, MA, United States
Objectives: Desmoid tumors are uncommon neoplasms characterized by clonal proliferation of myofi broblasts that do not metastasize, but often exhibit an infi ltrative pattern and functional impairment. When desmoids arise in the intestinal mesentery, surgical resection is seldom possible without life-altering loss of intestinal function. The objective of this study was to evaluate a multidisciplinary strategy to care for patients with mesenteric desmoid tumors.
Methods: We undertook a retrospective review of the clinical management of 52 consecutive patients treated for desmoids of the intestinal mesentery from January, 2001 to August, 2006. A multidisciplinary treatment plan was developed based on primary disease extent, tumor behavior, and resectability. Patients with stable but unresectable disease were observed without treatment (n=4). Patients with stable, resectable disease underwent surgery (n=8). Patients with progressing, resectable disease underwent surgery (n=28), patients with unresectable progressing disease received chemotherapy (n=12), most commonly liposomal doxorubicin, followed by surgery if chemotherapy rendered the disease resectable (n=6).
Results: At a median follow-up of 50.0 months (range 4.6-212), 50 patients (96%) have disease control, with either no recurrence or radiographically stable disease. No patient requires total parenteral nutrition.
Conclusions: These data indicate the extent of disease, tumor behavior and resectability are important factors in when defi ning a treatment plan for mesenteric desmoid tumors. A multidisciplinary approach of surgery combined with chemotherapy is an effective and function-sparing strategy for managing this disease.

#35057 ACTIVITY OF MEDICAL THERAPY (METHOTREXATE + VINBLASTINE/VINORELBINE OR TAMOXIFEN) IN DESMOID FIBROMATOSIS (DF): RETROSPECTIVE ANALYSIS OF 79 PATIENTS FROM A SINGLE INSTITUTION.
Palma Dileo, Claudio Piovesan, Marianna Silletta, Elisa Puma, Roberta Sanfilippo, Elisabetta Pennacchioli, Marco Fiore, Alessandro Gronchi, Paolo Giovanni Casali
Istituto Nazionale Tumori, Milan, Italy; Campus Biomedico, Rome, Italy
Objectives: DF is a rare neoplasm, characterized by clonal proliferation of myofi broblasts, which can arise from the abdominal wall, mesentery or other extra-abdominal locations. Several medical treatments have been employed in the management of DF, including anti-estrogens (i.e. tamoxifen, TAM), nonsteroidal anti-infl ammatory drugs (NSAIDs), chemotherapy (Methotrexate (MTX) + Vinblastine or Vinorelbine (VBL/VNB).
Methods: The dataset of the Istituto Nazionale Tumori, Milan, was analyzed from 1977 to 2004. We focused on antitumor activity of MTX + VBL/VNB or TAM. 49/79 pts were females, and age ranged from 3 to 64 years; of these, 39/79 pts received MTX + VBL/VNB (every 10 days), and 20/79 received TAM (10-60mg/d). Tumor response was assessed in all pts. Of note, 8/11 pts with Gardner’s syndrome or FAP had extra-abdominal locations.
Results: MTX+VBL/VNB was administered for a median of 27 courses. As of February 2008, out of 39 pts who received chemotherapy, 11 (28%) had PR, 24 (61%) had SD exceeding 6 months. Out of 20 pts treated with TAM, 1 (5%) had CR, 2 (10%) had PR, 11 (55%) had SD exceeding 6 months. All 5 pts who progressed on TAM responded to MTX+VBL/VNB.
Conclusions: This retrospective analysis confi rms that MTX + VBL/ VNB is associated with interesting response rates and prolonged SD. TAM may give tumor responses, occasionally major, as well as prolonged SD. Both treatments are of interest in a non-metastatizing disease, marked by a variable natural history. Well tolerated medical therapies may well be resorted to during progressive phases.

34887 - WIDE RESECTION WITH RADIATION THERAPY OF EXTRA-ABDOMINAL DESMOID TUMORS
Anthony D. Uglialoro, MD; Francis R. Patterson, MD; Meera R. Hameed, MD; Charles S. Cathcart, MD; Joseph Benevenia, MD
New Jersey Medical School, Newark, NJ, United States
Objectives: The approach to treatment of extra-abdominal desmoid tumors with surgical resection alone has resulted in control rates from 50-70%. The use of radiation therapy has shown a local control rate in some series up to 85%. The purpose of this study is to describe the effectiveness of resection-radiotherapy for extra abdominal desmoid tumors.
Methods: We performed a retrospective chart review of 25 consecutive patients who presented with a total of 28 extra-abdominal desmoid tumors. Patients were included if the following criteria was met: 1) histologically proven diagnosis of extra-abdominal desmoid tumor, 2) the lesion was resected with a wide margin allowing limb salvage, and 3) no contraindication to radiotherapy. Functional analysis of the limb was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system.
Results: 17 patients with 19 tumors met the above criteria. Mean age at diagnosis was 23.6 years in 10:9 M:F ratio with a mean follow up of 3 years. Patients were followed with serial clinical exams & MRI of tumor sites. 6, 10, and 3 patients were treated with brachytherapy post-operatively, EBRT, or both respectively. Of the 16 patients with negative margins of resection, 2 suffered local recurrence and one of which had an extensive chronic history of intra- and extraabdominal desmoids tumors. No other complications were noted in this series for a local control rate of 89.5 %. The average MSTS score was 29/30 (96.7%)
Conclusions: The role of surgery, radiotherapy, chemotherapy, hormonal therapy, and other treatments for extra-abdominal desmoid tumors is not well defi ned. When a wide margin and radiotherapy can be performed with limb preservation surgery, our local control and complication rate compares favorably to most other methods

35048 - ANALYSIS OF FACTORS INFLUENCING LOCAL CONTROL OF DESMOIDS TUMOURS
Eelco de Bree; Ronald Keus; Frits van Coevorden The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands;
Arnhem Radiotherapy Institute, Arnhem, Netherlands
Objectives: Although desmoid tumours, also called aggressive fibromatosis, are histologically benign, they exhibit a locally malignant behaviour and are notorious for a high incidence of local recurrence. The experience of a single institute is reviewed to determine the risk factors for local disease recurrence and progression.
Methods: Retrospectively, 147 patients were identifi ed to have been treated for recurrent or residual desmoid tumours in our institute during the last 35 years. Potential prognostic factors for local tumour control failure, including gender, age (with various cut off points), size (with various cut off points), presentation (primary or recurrent), site (extremities, head and neck, abdominal wall, other trunk or intra-abdominal), treatment (surgery only, radiotherapy only, surgery plus radiotherapy or other) and margins (positive or negative), were analyzed for their signifi cance using the log-rank test for Kaplan-Meier time to local tumour control curves.
Results: After a median follow-up period of 86 months (mean 102, 1-327) the overall 5- and 10-years local tumour control rate were 87% and 85%, respectively. Gender, age, presentation and treatment were not of prognostic signifi cance. Positive margins (p=.015) as well as extremity and intra-abdominal localizations (p=0.043) were associated with increased probability of tumour recurrence or progression. There was a trend for tumours larger than 6 cm (p=0.091) to be associated with worse local tumour control.
Conclusions: Various local treatment modalities provide local disease control in the majority of cases (87% at 5 years). Positive margins and extremity or intra-abdominal localizations were associated with the highest probability of tumour control failure.

35088 - DOES PRIOR CONTAMINATED RESECTION INCREASE LOCAL RECURRENCE FOR DESMOID FIBROMATOSES?
Ernest U. Conrad; Jason Weisstein
Univeristy of Washington, Seattle, WA, United States
Objectives: Desmoid fi bromatosis are considered to be benign tumors, but are locally aggressive and have high local recurrence rates. Treatment approaches, which include surgery plus radiation therapy are controversial for the reduction of local recurrence and morbidity.
Methods: We have retrospectively reviewed our results with patients (N=75) diagnosed with desmoid fi bromatosis tumors from June 2001 ? June 2008.
Results: These patients account for 4% of all the soft tissue tumors seen by our multidisciplinary sarcoma service. Of the patients who received all their treatment at our institution (N=44), 70% were female (N=31) with a median age of 36.5 (18 ? 82) years at diagnosis. The majority presented in the extremity (N=24, 32%), followed by the abdominal wall, retroperitoneum, and thorax (N=12 each, 16%), the pelvis (N=8, 11%), and lastly the spine (N=7, 9%). Almost 91% (N=40) were treated with surgical excision and of those 50%( N=20) had positive surgical margins. Sixty-eight percent (N=30) of the total treated group (N=44) received adjuvant radiation therapy and of those treated 47% (N=14) did not have a local recurrence, 16% had a local recurrence (N=5) and the remaining 11 patients (37%) were lost to follow-up. In the group that did not receive radiation therapy, 42% (N=5) did not have a local recurrence, one patient (8%) had a local recurrence and the remaining 6 (50%) were lost to follow-up.
Conclusions: A combination of radiation and surgery may improve local control, while prior contaminated resection does not seem to have an effect on local control based on this preliminary dataset.

35093 - DESMOIDS TUMORS: USING PET IMAGING TO DISTINGUISH RISK OF RECURRENCE
Ernest U. Conrad; Jason Weisstein; Janet F Eary
Univeristy of Washington, Seattle, WA, United States
Objectives: Desmoid tumors have variable aggressive behavior with respect to local recurrence. [F-18] - FDG PET imaging may provide another means of evaluating tumor behavior preoperatively.
Methods: We have retrospectively reviewed our results with
Results: The mean age and local recurrence was similar between two study groups separated by time, Cohort 1: 1982 1998 and Cohort 2: 2001 2007. Local recurrence was similar between both cohorts, 27% vs. 22%. However, when divided by two treatment groups local recurrence with surgical resection only was 47% (cohort 1) and 30% (cohort 2) vs. surgical resection + radiation therapy was 19% (cohort 1) and 25% (cohort 2). In Cohort 1 patients were treated with radiation therapy 64.6% of the time and in Cohort 2, 61.4% of the time. Anatomic location and patient ages had similar distribution in both groups. A subset in Cohort 2 were imaged using [F-18] FDG (N=12) with correlation to local recurrence.¯¯
Conclusions: Patients with higher SUVmax had a trend toward a higher risk of local recurrence and a shorter interval in time to recurrence. PET imaging may be useful in evaluating the risk of recurrence for desmoids tumors. This work is supported by NIH/NCI CA R01 65537.

35158 - MELOXICAM, A COX-2 INHIBITOR, AS A NONSURGICAL THERAPY FOR DESMOID TUMORS
Yoshihiro Nishida; Satoshi Tsukushi; Yoji Shido; Kozo Hosono; Naoki Ishiguro
Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
Objectives: A prospective, non-randomized consecutive analysis of therapeutic outcomes of meloxicam for the patients of desmoid tumors, compared with retrospective control patients with surgical treatment.
Methods: Fifteen patients with histologically diagnosed as desmoid tumors were treated with meloxicam (10mg/day). The mean age of the patients was 51 years old (20-86) with 5 males and 10 females. An average follow up was 31 months. Size of the tumors was determined with MR imaging every 6 months, and effi cacy of meloxicam was evaluated as CR, PR, SD, and PD. Treatment was discontinued for patients with severe complications or with evaluation of PD. Twenty patients with surgical treatment were retrospectively reviewed with an average 4.9 year follow-up (2.2-11). The mean age was 36 years old (7-62) with 8 males and 12 females.
Results: There were 2 abdominal desmoid and 13 extra-abdominal desmoid tumors in meloxicam group. COX-2 over-expression was observed with immunohistochemical methods. Patients outcome was evaluated as PR in 6, SD in 6, PD in 3. Although gastritis occurred in 2 patients, there were no severe complications. Reduction of ADL was not observed in 3 patients with PD evaluation. In surgical treatment group, 11 patients (55%) recurred at mean follow-up of 15 months.
Conclusions: Meloxicam might be able to regulate the aggressiveness of desmoid tumors.

34946 - CLINICAL OUTCOMES OF SYSTEMIC THERAPY FOR PATIENTS WITH DESMOID TUMORS Veridiana P. Camargo; Mary Louise Keohan; David R. D’Adamo; Cristina R. Antonescu; Mark A. Edgar; Samuel Singer; Murray F. Brennan; Robert G. Maki Memorial Sloan Kettering Cancer Center, New York, NY, United States
Objectives: We examined outcomes of patients with desmoid tumors receiving systemic therapy at a single institution, to provide a basis for examination of newer agents.
Methods: Retrospective chart review of 682 patients with desmoid tumors (1982-2006) from a prospectively collected sarcoma database. The activity of NSAIDs was not addressed. Patients without measurable disease, those receiving therapy we could not document, and those receiving prophylactic therapy were excluded.
Results: A total of 69 patients received 163 lines of well-documented systemic therapy starting before 1/1/2007. Nine patients died, 7 of progressive disease/surgical complications, and two with Gardner syndrome-related malignancies. Demographics: 45 females (65%), median age 30 (range 15-75), 21 with Gardner syndrome (30%), median follow-up 68 months, and median of 2 lines of therapy (1-7). Intra-abdominal primary location was most common (28/69=41%). Tamoxifen, doxorubicin (including Caelyx/Doxil®), imatinib, and methotrexate combinations were most commonly used. Four partial responses were observed with anthracyclines (42 courses administered), 2 with hormonal therapy (32 courses), and 1 with imatinib (35 courses), for 7 PR (response rate 4%). In aggregate, median progression-free survival (PFS), symptomatic or radiologic, was 8.9 months (range 0.2 to 117+). Univariate and multivariate analyses showed only anthracycline-based therapy as demonstrating a trend toward statistical signifi cance for improved PFS (p=0.06).
Conclusions: Anthracycline-containing regimens, hormonal therapy, and tyrosine kinase inhibitors have modest activity against desmoid tumors. The choice of therapy for these morbid and potentially fatal tumors should balance the effi cacy of treatments with their short- and long-term side effects.

034852 SUCCESSFUL TREATMENT OF FIBROMATOSIS WITH HYDROXYUREA: ANALYSIS OF 20 PEDIATRIC CASES (details) Naomi I Balamuth, Richard B Wormer
Childress Hospital of Philadelphia, Philadelphia,PA. United States: University of Pennsylvania, Philadelphia, PA. United State
Objectives: While surgical excision is generally the initial therapy for aggressive fibromatosis, many tumors, are either unresectable or recur following excision. Radiotherapy and a variety of chemotherapy regimens have been used in these patients, all with considerable toxicity. We reviewed our institutional experience in treating aggressive fibromatosis with hydroxyurea.
Methods: We retrospectively reviewed the charts of 16 pediatric fibromatosis patients treated with hydroxyurea. Patients were treated with an initial dose of 20 mg/kg, increasing as ANC permitted, with an intended treatment duration of one year.
Results: We identified 20 tumors (8 extremity, 7 torso. 4 head/ neck, 1 abdominal) in 16 patients. The mean age at initiation of hydroxyurea therapy was 9.7 years. The mean administered dose was 30 mg/kg/day. Patients were grouped according to the Intergroup Rhabdomyosarcoma Study Group (IRS) system. Prior therapy (if any) included various chemotherapeutic, regimens, radiation and surgery. Four out of five (80%) of IRS Group I/II patients maintained remission with hydroxyurea. Of the IRS Group III/IV patients, 4/14 (29%) had a complete or partial response, 7/14 (50%) had stable disease, and 3/14 (21%) had progressive disease. Patients experienced minimal to no symptomatic toxicity with this regimen.
Conclusions: Hydroxyurea seems an active single agent in the treatment of aggressive fibromatosis. Larger studies are needed to examine its efficacy further, and to test it in combination with other known active agents against this difficult disease.