Treatment Of Aggressive Fibromatosis Research Articles

Imatinib in Patients with Aggressive Fibromatosis and Pigmented Villonodular Synovitis: A Systematic Review

Introduction: We undertook a systematic review of the literature to determine theefficacy and safety of Imatinib in the restriction of activity and effective treatment ofpatients with aggressive fibromatosis (AF) and pigmented villonodular synovitis (PVNS)and their recurrence.Method: We searched studies in the PubMed and Cochrane collaborative library at alllevels from 2010 to April 2019. Two independent reviewers evaluated the articlesaccording to the predefined criteria and extracted the related data. Primary outcomesassociated with tumor size shrinkage, relapse and overall survival along with secondaryoutcomes such as pain, quality of life, and side effects were investigated.Results: 112 studies were evaluated out of which only 6 studies that covered originalstudies and case reports were entered into this systematic review. A total of 79subjectshad participated in these six studies with an age range of 22 to 41 years old. In fivestudies, participants had a primary tumor and in one research they reported relapse. Therecommended dose was 400 mg/day, which was usually continued for 4 to 12 months.The tumor size shrinkage and low side effects of drugs have been reported.Conclusion: According to the results, no systemic treatment for PVNS and AF has beenapproved so far, but many studies have demonstrated the efficacy of Imatinib in thetreatment of these diseases. However, further studies are required for optimal treatmentand combined therapies.

Research Progress of Multidisciplinary Comprehensive Diagnosis and Treatment of Aggressive Fibromatosis

Research Progress of Multidisciplinary Comprehensive Diagnosis and Treatment of Aggressive Fibromatosis

Radiotherapy in the treatment of aggressive fibromatosis: experience from a single institution

BackgroundDesmoid-type fibromatosis is a rare, potentially locally aggressive disease. Herein we present our experience in the treatment with radiotherapy.Methods and materialsIn total 40 patients who received 44 treatments from 2009 to 2018 at the Heidelberg University Hospital with photons (N = 28) as well as protons (N = 15) and carbon ions (N = 1) were investigated. The median age at radiotherapy was 41 years [range 8–78]. Familial adenomatous polyposis (FAP) was confirmed for nine patients and 30 had a unifocal desmoid tumor. The localizations were abdominal wall, abdominopelvic cavity, thoracic wall, extremity, head and neck and trunk. The median prescribed dose was 54 Gy/ Gy (RBE) [range 39.6–66, IQR 50–60]. Eleven treatments were performed at the time of first diagnosis; 33 at the time of progression or recurrence. Post-operative radiotherapy was performed in 17 cases. The median planning target volume was 967 ml [84–4364 ml, IQR 447–1988]. Survival analysis was performed by the Kaplan-Meier Method.ResultsThe median follow-up time was 32 months [1–153]. At the end of the follow-up interval all patients but one were alive. The estimated local progression free survival of the treated lesion in 3 and 5 years was 76.4% and 63,8%, respectively. The progression-free survival in 3 and 5 years was 72.3 and 58.4% and the overall survival was 97.4 and 97.4%, respectively. In case of macroscopic tumor (N = 31) before radiotherapy a partial remission was observed in 12 cases (38.7%) and a complete remission in 4 cases (12.9%). Progression was observed in 13 (29.5%) cases, predominantly at the margin of the planning target volume (PTV, N = 5, 38,4%) followed by progression within the PTV (N = 4, 30.8%). In univariate analysis multifocal localization was associated with impaired progression-free survival (p = 0.013). One patient developed a grade V gastrointestinal bleeding, otherwise no acute toxicity >°III was observed. Late toxicity was depending on the localization of the desmoid tumor and was especially severe in patients with FAP and abdominopelvine desmoids including gastrointesinal fistula, perforation and abscess.ConclusionRadiotherapy in the treatment of desmoids can lead to long term control. Treatment of patients with abdominopelvine desmoids should be avoided, as the risk of higher-grade complications is substantial.

Management of Abdominal Wall and Intraabdominal Fibromatosis with Multi-organ Involvement: a Case Report

Desmoid tumors are uncommon, with an overall reported incidence of 2–5 per million population. They can be seen anywhere in the body. Desmoid tumors are associated with familial adenomatous polyposis especially with Gardner syndrome. In this study, we performed surgery for an abdominal mass involving the bladder, sigmoid colon, ileum, omentum, and rectus abdominis muscle macroscopically. A 50-year-old woman complained about abdominal distention of 1-year duration and abdominal pain for 2 months. In physical examination, tenderness was found at the lower quadrants of the abdomen and the suprapubic region. Computed tomography (CT) revealed a 43 × 43-mm mass lesion in the soft tissue densities. Magnetic resonance imaging (MRI) revealed a 43-mm lesion most likely a cyst or a sigmoid mass associated with sigmoid colon. Tumor was totally resected and pathologically diagnosed as fibromatosis. Differential diagnosis of the abdominal desmoid tumors could be difficult if the tumor is not settled in anterior preperitoneal space typically. Primary treatment of aggressive fibromatosis is surgery. Depending on the experience of the surgeon, recurrence rate varies between 25 and 65%. Radiotherapy is performed as adjuvant treatment for local control of the tumor or can be performed if the disease is extensive and local excision is not possible with surgery.

Aggressive fibromatosis of head and neck: Considerations on the optimal treatment method on the basis of case report

Abstract Introduction The term fibromatosis refers to proliferation of fibrous tissue in the form of irregular nodules or soft tissue sarcoma. It is characterized by local malignancy with tendency to recurrence, significant hypertrophy of the mature connective tissue and lack of the ability to form distant metastases. Pathological lesions originate from fascial, muscle and tendinous tissue. Aim The aim of this work is to analyze the efficacy and safety of the selected methods of treatment of aggressive fibromatosis on the basis of the presented case. Case study A five-year-old boy was admitted to the Department of Otolaryngology of the Provincial Specialist Children’s Hospital in Olsztyn due to right sided cervical mass. Histological examination of biopsy material revealed aggressive fibromatosis. The child was previously treated for two years with systemic chemotherapy with methotrexate, vinblastine, vincristine, imatinib and tamoxifen with no improvement. Surgical tumor removal was performed on February 14, 2014. During the 18-month observation period no signs of tumor recurrence were observed. Results and discussion In the treatment of aggressive fibromatosis various therapeutic methods are used, including radiotherapy, chemotherapy and surgery. The effects of chemotherapy and radiotherapy are frequently unsatisfying. These methods are associated with numerous complications and side effects, thus mode of treatment should be considered individually for each patient. In case of the presented patient surgical tumor removal was the best and the most effective treatment method. Conclusions Surgery should be a treatment of choice, whereas chemotherapy and radiotherapy should be considered as alternative or complementary methods in the treatment of aggressive fibromatosis.

Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention.

BackgroundThe efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor.Design and methodsGRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization.DiscussionThis study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression.Trial registrationThe GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number 4714.

Long-term outcomes of 47 patients with aggressive fibromatosis of the chest treated with surgery

AimsThe purpose of the study was to review a large series of chest aggressive fibromatosis (AF) cases with an emphasis on the outcomes of different degrees of resection and the value of postoperative radiotherapy. Materials and methodsThe records of patients with chest AF treated at our hospital from 1982 to 2014 were retrospectively reviewed. Recurrence rates and non-disease survival (NDS) times were compared between the R0, R1, and R2 resection groups. ResultsForty-seven cases of chest AF were treated during the study period (21 men, 26 women), with an average age at diagnosis of 40 years (range, 9–77 years). One patient died before surgery, and 46 patients received a total of 85 resections. Forty-one patients had complete follow-up data, and the average follow-up time was 125.6 months (range, 11–524 months). Recurrence rates were 6.7%, 92.9%, and 100% for the R0, R1, and R2 resection groups, respectively, and the R0 recurrence rate was significantly lower than the R1 and R2 rates (both P values < 0.001). The NDS time of the R0, R1, and R2 groups was 80.3 ± 64.8, 23.6 ± 38.7, and 9.8 ± 10.8 months, respectively; the NDS time of the R0 group was significantly longer than that of the R1 and R2 groups (both P values < 0.01). Within each resection type, no significant differences were found in the recurrence rates of patients having surgery alone compared with those receiving surgery and radiotherapy (all P values > 0.05). ConclusionR0 resection is the most effective treatment for chest AF. Postoperative radiotherapy did not reduce the recurrence rate.

Prognostic Value of CTNNB1 Gene Mutation in Primary Sporadic Aggressive Fibromatosis

Aggressive fibromatosis (AF) comprises tumors with a varying biological behavior. Genetic tumor characteristics may be predictive of recurrence; hence, the prognostic value of three specific mutations on the CTNNB1 gene was evaluated in relation to known clinicopathologic risk factors in patients with primary, sporadic AF. In a multi-institutional retrospective cohort study of patients with primary extra-abdominal and abdominal wall AF who underwent surgical treatment, the original pathology specimens were reviewed for the presence of a T41A, S45F, and 45P mutations on the CTNNB1 gene. For these mutations, the risk of recurrence was analyzed by the Kaplan-Meier method with log-rank test. Univariable and multivariable Cox regression was performed to calculate hazard ratios. A total of 101 patients were analyzed. During a median follow-up of 41months, 17 recurrences were detected; the cumulative 5-year recurrence rate was 22.8%. A specific CTNNB1 mutation was found in 76 patients, with the majority of patients having a T41A mutation (n=49). CTNNB1 mutations were associated with the risk of recurrence: the presence of a S45F mutation was associated with a 5-year cumulative risk of recurrence of 63.8% (P<0.001). Multivariable analysis showed that young age and S45F mutation were independent risk factors (P=0.011 and P<0.001). The presence of specific CTNNB1 mutations was predictive for recurrence in patients after surgical treatment for primary, sporadic extra-abdominal and abdominal AF. A S45F mutation increased the risk of recurrence significantly.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy.

An analysis of the treatment of aggressive fibromatosis: Review of cases

An analysis of the treatment of aggressive fibromatosis: Review of cases

A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis.

10589 Background: There have been reports on responses and prolonged disease stabilizations with imatinib which may be associated with PDGFR-β pathway and KIT mutation in the treatment of aggressive fibromatosis (AF). Sunitinib has not only PDGFRs, KIT, and FLT3 inhibiting activity, but also VEGFRs blockade as antiangiogenesis. The aim of this study is to evaluate the efficacy and safety of sunitinib for patients with advanced AF. Methods: Nineteen patients with pathologically proven AF were accrued between Jun 2008 and Mar 2012. Sunitinib was administered with 37.5 mg/day for 4 weeks without break, comprising one cycle. Primary endpoint was response rate. Results: Ten (53%) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63.2%), and AF associated with familial adenomatous polyposis was observed in 10 (52.6%). With a median 6 cycles per patients (range, 1-47 cycles), 5 (26.3%) achieved a partial response and 8 (42.1%) had stable disease; the overall response rate was 26.3% (95% CI, 6.3-45.7) in intention-to-treat analysis. With median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year progression-free survival and overall survival were 74.7% and 94.4%, respectively. Grade 3 or 4 adverse events of sunitinib with frequency &gt; 5% of patients included neutropenia (33.3%), diarrhea (5.3%), and hand-foot syndrome (5.3%). In 3 patients out of 12 patients with mesenteric AF, mesenteric mass bleeding (n=1), bowel perforation (n=1), and bowel fistula (n=1) with tumor mass necrosis, were observed during an early period of sunitinib. Conclusions: Sunitinib showed potential antitumor activity and was relatively tolerated in patients with AF, especially non-mesenteric AF. Further investigation of sunitinib treatment is necessary in patients with AF.

Relationship of FAP-alpha, ADAM12, WISP1, and SOX11 expression to tumor activity in aggressive fibromatosis: Demonstration of heterogeneity within and between cases.

10560 Background: Aggressive fibromatosis (AF) represents a group of tumors with an unpredictable clinical course and is characterized by a monoclonal proliferation of myofibroblasts. The optimal treatment for AF is unclear. In earlier gene expression studies we identified four genes, ADAM12, WISP1, SOX11, and FAP-alpha, that were uniquely overexpressed in AF compared with 16 different normal tissues. This study was designed to examine the expression of these four proteins in AF. Methods: Immunohistochemistry (IHC) was performed in 29 cases of AF, and analyzed by a pathologist with expertise in the field. Automated imaging analysis was performed to independently quantify IHC staining, nuclear size, and nuclear chromatin density. Nuclear size was determined on control slides. Slides were scanned using ScanScope XT (Aperio) and images were divided into tiled regions of interest (ROIs) for measurements. A nuclear chromatin density ratio (CDR), defined as the measure of nuclear area with light staining divided by nuclear area with dark staining, was quantified as a surrogate for nuclear activity. To compare the image analysis with pathologic examination, an operational definition of “morphologic tumor activity” (MTA) was determined by a pathologist using a scale of 1 (inactive), 2 (probably inactive), 3 (probably active), and 4 (active) on a random set of 322 ROIs. The MTA score was then correlated with the CDR. We also assessed the relationship of CDR to IHC staining intensity for each of the four proteins in ~26,000 ROIs derived from all 29 AF samples. Results: Different areas of AF cases had different degrees of MTA. The expression of the four proteins generally correlated with the areas of tumor that were pathologically more “active.” Staining was more intense in areas with larger more open nuclei suggesting “more active” regions. There was a significant correlation between MTA and log [CDR] (0.46, p&lt;0.001). Conclusions: The results confirm, on the protein expression level, our earlier gene expression results, and demonstrate the regional variation of tumor activity within and among AF cases.

The treatment of desmoid tumors: a stepwise clinical approach

Aggressive fibromatosis (AF) is a monoclonal proliferative disease but does not metastasize and does not dedifferentiate to a high-grade malignancy in case of recurrence. Biopsy is usually necessary to confirm the diagnosis. A hallmark is its apparent unpredictable clinical course producing a large heterogeneity even with an indistinguishable morphology. Additional studies of the molecular determinants of desmoid behavior are needed to guide selection of the various therapeutic modalities. During the last 10 years, the treatment of AF has evolved and the role of routine, aggressive first-line treatment (radiotherapy and surgery) is now debated. If a wait-and-see policy is used at initial presentation, it is observed that >50% of patients will have relatively indolent disease. Aggressive treatments that take their indications from retrospective studies should be re-evaluated in the light of new data. The objective of this article is to propose an algorithm that commences with more conservative approaches before treatments that have associated long-term morbidity, the more aggressive therapies being reserved only for those who really need it.

1479PD - Multi-Center Phase II Study of Sunitinib in Patients with Advanced Aggressive Fibromatosis (Desmoid Tumor)

ABSTRACT Background There have been reports on the efficacy of imatinib, a multi-targeted tyrosine kinase inhibitor, in the treatment of aggressive fibromatosis (AF, also known as desmoid tumor) by inhibiting PDGFRA and PDGFRB rather than KIT. Sunitinib has not only PDGFRs, KIT, and FLT3 inhibiting activity but also VEGFRs blockade as antiangiogenesis. The aim of this study is to evaluate the efficacy and safety of sunitinib for patients with AF. Methods This is a multi-center, phase II study. Nineteen patients with pathologically proven AF were accrued between Jun 2008 and Mar 2012. Sunitinib was administered with 37.5 mg/day for 4 weeks without break, comprising one cycle. Primary endpoint was response rate. Results Ten (53%) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63%), and AF associated with familial adenomatous polyposis was observed in 9 (47%). The median tumor size was 5.0 cm (range, 2.0-14.2), and 8 patients (42.1) had multifocal tumor lesions. Of the 15 patients who received two or more cycles of treatment, 6 (40%) required dose reductions. With a median 5 cycles per patients (range, 1-47 cycles), 5 (26%) achieved a partial response and 8 (42%) had stable disease; the overall response rate was 26% (95% CI, 6.3-45.7). With median follow-up time of 11.8 months (range, 1.4-43.7), the 2-year progression-free survival and overall survival were 70% and 100%, respectively. Of 10 patients in whom thyroid function test were checked, 1 (10%) had grade 2 hypothyroidism and 5 (50%) grade 1. Grade 3 or 4 adverse events of sunitinib with frequency > 5% of patients included neutropenia (33%), diarrhea (5%), and hand-foot syndrome (5%). Intra-abdominal tumor perforation with cystic necrosis within first cycle of sunitinib occurred in 3 cases; 2 cases underwent palliative tumor resection and 1 case recovered with medical treatment. There was no treatment-related death. Conclusion Sunitinib was well-tolerated and showed promising antitumor activity in patients with AF. Further investigations on clinical and translational researches of sunitinib in these patients are warranted. Disclosure All authors have declared no conflicts of interest.

Clinical management of pediatric aggressive fibromatosis involving the mandible

Pediatric aggressive fibromatosis (AF) is a rare, benign tumor with locally infiltrative growth. Therefore, how to prevent reoccurrence while maintaining the mandible contour and continuity as much as possible is very important when the mandible is involved. We selected 10 pediatric patients with AF involving the mandible in our department between January 2001 and December 2011. Patient clinical data, including patient characteristics, symptoms at presentation, management, and treatment outcome, were reviewed. Patients' ages ranged from 3 to 16 years with six males and four females. According to imaging, there were three cases where the tumor adhered to the mandible; the periosteum was resected with the tumor, followed by cryotherapy or cauterization. Another five cases involved the destruction of the periosteum and the cortical plate. Resection of the involved mandible with the tumor was performed, and the margin was trimmed. In the last two cases, the tumor had invaded the whole ramus, and the immediate iliac graft was operated on after resecting the lesions. Neither radiotherapy (RT) nor chemotherapy was used. There was no recurrence or contour defect of the face. The function of the mandible was not affected, and only one case showed a slight limitation when opening the mouth. For the treatment of pediatric AF, we recommend complete tumor resection. As for the involved mandible, preserving the mandible contour and continuity as much as possible and providing adjunctive therapy, such as cryotherapy or cauterization, are vital. RT is not recommended.

The clinical characteristics and prognostic factors of aggressive fibromatosis in 142 patients

Objective Aggressive fibromatosis is a rare kind of soft tissue tumor and was evaluated by few large studies. This study was to evaluate the clinical characteristics and identify the prognostic factors of this disease. Methods One hundred and forty-two patients with aggressive fibromatosis treated from January 1983 to August 2009 in Tianjin Medical University Cancer Hospital were retrospectively reviewed.The prognostic value of clinical and treatment factors was analyzed. Univariate analysis was performed with Log-rank test and Multivariate analysis was performed with Cox regression model. Results The follow-up rate is 93.7% and the median follow up time was 54 months (range,6 -208 months). Sixty-three patients had a minimum follow up time of 5 years and 6 patients had a minimum follow up time of 10 years. The male/female ratio was 1/1.84. The disease was most popular in women aged from 18 to 35 years old. The disease frequently occurred in the trunk (55.6%) and extremity (31.7%). All patients received surgery,and 46 received radiotherapy. The 5-year and 10-year local recurrence rates were 24. 4% and 31.1%,respectively. The 5-year and 10-year overall survival rates were both 99. 3%. Univariate analysis revealed that factors correlated with local recurrence were tumor size ( χ2 = 4. 37, P = 0. 037 ) and margin status (χ2 = 12. 36,P =0. 002). Multivariate analysis revealed that margin status was an independent risk factor (RR = 2. 219; χ2 = 9. 47,P = 0. 002) and radiotherapy was an independent protective factor ( RR = 0. 360;χ2 = 4. 95, P = 0. 026 ) for disease recurrence. When radiotherapy was delivered, the 10-year local recurrence rate decreased from 70. 1% to 20. 7% in patients with positive margin ( χ2 = 4. 22, P = 0. 040 )and decreased from 19.8% to 10.4% (χ2= 0.90, P= 0.344) in patients with negative margin.Conclusions Radical resection is the mainstay of treatment for aggressive fibromatosis. Postoperative radiotherapy can reduce the recurrent rate for patients with positive margin. In patients with negative margin,the role of radiotherapy should to be further evaluated in large clinical trials. Key words: Aggressive fibromatosis/surgery; Aggressive fibromatosis/radiotherapy; Prognosis

Treatment of Aggressive Fibromatosis: the Experience of a Single Institution

Aims Aggressive fibromatosis is a locally aggressive infiltrative low-grade tumour, although pathologically benign, and it does not metastasise, yet it can cause serious local distressing symptoms by virtue of local destruction and impairment of local function. The aim of this study was to emphasise the role of radiotherapy and adequate surgery in the treatment of fibromatosis in patients presenting with newly diagnosed or recurrent disease and to analyse our treatment results over 15 years for this rare tumour type. Materials and methods Fifty-four patients with confirmed diagnosis of aggressive fibromatosis treated at King Faisal Specialist Hospital between 1990 and 2006 were identified from our local cancer registry. Forty-seven patients had surgery: complete resection (R0) in 20 patients, incomplete surgery (R1/2) in 27 patients, and seven patients had biopsy only. Forty-five patients were treated with radiotherapy: 38 patients were treated with postoperative radiotherapy, three patients were treated with preoperative radiotherapy and four patients had radiotherapy as the only treatment. The radiotherapy dose ranged between 45 and 60 Gy (median 50.4 Gy). Three patients did not receive any form of treatment apart from biopsy, but were still included in the final analysis. Results Fifty-two per cent (28/54 patients) of our patient population had tumour recurrence when first presented to King Faisal Specialist Hospital. The median age was 29.5 years (range 2–63 years). The most common site of involvement was the extremities (28 patients). Among the 54 patients (with primary and recurrent presentation) there were 10 local recurrences, all of which were within the original primary site. The 5-year progression-free survival and overall survival rates for the whole group were 75 and 95%, respectively. Univariate and multivariate Cox regression analysis showed that the depth of invasion significantly affected progression-free survival. Conclusion Aggressive fibromatosis is effectively treated with surgery and postoperative radiotherapy. Patients first presenting with tumour recurrence may still have local tumour control comparable with newly diagnosed patients.

Treatment of aggressive fibromatosis with pegylated liposomal doxorubicin: The Royal Marsden Hospital experience

10519 Background: Aggressive fibromatosis (AF) or desmoid tumors are monoclonal proliferations which are locally invasive but do not metastasise. Sporadic tumors are usually associated with mutations in the beta-catenin gene CTNNB1whereas those occurring in the context of familial adenomatous polyposis usually have inactivating mutations in APC. Histologically they are characterised by nuclear expression of beta-catenin. When surgery and radiotherapy are not applicable or fail to control the disease, systemic treatment with anti-oestrogens, non steroidal anti-inflammatory drugs (NSAIDs) and chemotherapy can be used. A variety of regimens are reported to have activity including methotrexate/vinblastine and doxorubicin/dacarbazine. Recent reports indicate that single agent pegylated liposomal doxorubicin (Caelyx, C) is also effective. Methods: Ten patients with AF received C between June 2006 and December 2008. C was administered intravenously at 50 mg/m2 over 1 hour every 4 weeks. Results: The female/male ratio was 9:1 and the median age at presentation was 39.5 years (range 18–53). All patients had progressive fibromatosis. Fifty percent had previously been treated with surgery/radiotherapy or both. All but one had previous systemic therapy which comprised tamoxifen/toremifene (6), NSAIDs (1), chemotherapy (1) and imatinib (1). C was well tolerated with mucositis (6/10), palmar-plantar erythema (4/10) and fatigue (2/10) being the main toxicities. A dose reduction to 40 mg/m2 was required in 50% of cases hence the optimal dose lies between 40 and 50 mg/m2. One patient is currently receiving treatment and is too early to assess. For the nine patients who have completed treatment the median number of C cycles was 6 (range 4–6). Objective response according to RECIST was achieved in 4/10 patients and in 5 patients the best response was stable disease. Clinical benefit (pain relief, improved mobility) was observed in all patients. The duration of response ranged from 4 to 28 months. Conclusions: This is the largest series of patients with AF receiving C presented to date. C as single agent therapy has acceptable toxicity and highly promising activity in unresectable AF and may provide long term clinical benefit in some patients. No significant financial relationships to disclose.

Outcome of Aggressive Fibromatosis Treated with Radiation Therapy

The purpose of this study is to report the clinical course and outcome in 7 patients with aggressive fibromatosis. Between the years 2000 and 2003, 7 patients who were treated with combined modalities were evaluated retrospectively. Patients' demographic information, including age and gender, tumour characteristics, surgical resection, and the use of radiotherapy were recorded and evaluated. The mean patient age was 34 years. The median time to follow-up was 15.5 months. Resection was performed with positive surgical margins in three cases. Three patients were evaluated as inoperable and one patient was treated with debulking surgery. All patients received radiation therapy with a median dose of 51 Gy. At follow-up, three patients had no evidence of disease, three patients were alive with disease, and one patient died 15 days after radiotherapy. Local control is the primary problem in aggressive fibromatosis. There is no appropriate treatment for aggressive fibromatosis and the type of treatment depends on tumour characteristics and location as well as patient characteristics.

Intraoperative Electron Radiotherapy (IOERT) in the Management of Aggressive Fibromatosis

Aggressive fibromatosis, also known as desmoid tumor, is an uncommon benign, fibroblastic proliferation with an infiltrating, locally aggressive growth pattern. As local recurrence rates remain high after surgery alone especially in margin-positive patients, and radicality of surgery is often compromised when weighed against function preservation, the addition of external beam radiotherapy (EBRT) is recommended by most authors. In recent years, evidence for a benefit of dose escalation especially in patients with residual disease after surgery is growing. Here we report our experience with intraoperative electron boost radiotherapy (IOERT) after surgery in the treatment of aggressive fibromatosis. Indication for IOERT and additional postoperative EBRT in the meaning of an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. Between 1997 and 2005 a total of 28 patients (male:10, female:18) underwent surgery and IOERT with a median dose of 12 Gy. Median age was 27 years (range 13–56 years). Resection status was negative but close margin (<5 mm) in 6 and microscopically positive in 11 patients. Macroscopic residual disease was present in 11 patients. Half of the patients presented in primary and recurrent situation respectively. Median tumor size was 9 cm. Twenty-two patients received additional EBRT with a median dose of 45 Gy (range 36–54 Gy). After a median follow up of 32 months (range 3–106) no disease-related deaths occurred. A total of five local recurrences were seen, three of them inside the IOERT fields, one inside the EBRT fields and one at the border of the EBRT fields. The resulting estimated 5-year local control rates overall and inside the IOERT fields were 74% and 85% respectively. Trends to improved local control were seen for young age (<25 years), female gender and negative margins, but none of these factors reached significance. If present, the extent of residual disease (microscopic or macroscopic) showed no impact on local control, neither did presentation in primary or recurrent situation, size or localisation of the disease. Perioperative complications were seen in six patients, in particular wound healing disturbances in five and venous thrombosis in one patient. Late toxicity was seen in four patients (lymph edema 2, ileus 1, disturbed limb function 1). Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity. Local dose escalation through IOERT in combination with moderate doses of EBRT resulted in high local control rates even in patients with macroscopic residual disease.