Activity of Sorafenib against Desmoid Tumor/Deep Fibromatosis

Departments of Medicine, Radiology, Pathology, and Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA.
Clinical Cancer Research (Impact Factor: 8.72). 03/2011; 17(12):4082-90. DOI: 10.1158/1078-0432.CCR-10-3322
Source: PubMed


Desmoid tumors (deep fibromatoses) are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are associated with morbidity and occasionally mortality. Responses of desmoid patients to sorafenib on an expanded access program led us to review our experience.
After Institutional Review Board (IRB) approval, we reviewed data for 26 patients with desmoid tumors treated with sorafenib. Sorafenib was administered at 400 mg oral daily and adjusted for toxicity.
Sorafenib was the first-line therapy in 11/26 patients and the remaining 15/26 had received a median of 2 prior lines of therapy. Twenty-three of 26 patients had shown evidence of progressive disease by imaging, whereas 3 patients had achieved maximum benefit or toxicity with chemotherapy. Sixteen of 22 (∼70%) patients reported significant improvement of symptoms. At a median of 6 months (2-29) of treatment, the best response evaluation criteria in solid tumors (RECIST) 1.1 response included 6/24 (25%) patients with partial response (PR), 17/24 (70%) with stable disease, and 1 with progression and death. Twelve of 13 (92%) patients evaluated by MRI had > 30% decrease in T2 signal intensity, an indirect metric for increased fibrosis and loss of cellularity. Eighty percent of patients with radiological benefit had extra-abdominal desmoids.
Sorafenib is active against desmoid tumors. A prospective, randomized clinical trial of sorafenib against other active agents is warranted. Loss of MRI T2 signal may be a useful surrogate for defining responses, but requires validation by examination of tumor pathology.

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    • "Desmoid-type fibromatosis (DTF), also known as desmoid tumor or aggressive fibromatosis, is a rare soft tissue neoplasm. It is locally invasive but without metastatic potential, and is slow-growing [1]. DTFs, which may be extra-abdominal, of the abdominal wall, or intra-abdominal, can arise from any fibrous connective tissues throughout the body [2], but the great majority occur unpredictably at sites of previous trauma, scarring, or irradiation. "
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    ABSTRACT: Desmoid-type fibromatosis (DTF) is an uncommon nonmetastatic fibrous neoplasm. Sporadic intraperitoneal DTF is rarely described in current literature. We herein report a case of DTF of unknown cause involving the pancreatic head. A 41-year-old man presented with recurrent epigastric pain and weight loss. An abdominal computed tomography scan showed a well-delineated solid cystic mass inside the pancreatic head. Pylorus-preserving pancreaticoduodenectomy was performed due to the patient's debilitating symptoms and suspected malignancy. The pathological examination revealed massive fibroblastic proliferation arising from the musculoaponeurotic tissues, consistent with a diagnosis of DTF. Immunohistochemical phenotyping determined positive immunoreactivity to vimentin and beta-catenin, but negative immunoreactivity to smooth muscle actin, CD117, CD34, or S-100, confirming the diagnosis of DTF. No local recurrence or distant metastasis was found during a 24-month follow-up. Radical resection is recommended as first-line treatment for pancreatic DTF. Long-term follow-up studies are required to establish the prognosis of pancreatic DTF.
    World Journal of Surgical Oncology 04/2014; 12(1):103. DOI:10.1186/1477-7819-12-103 · 1.41 Impact Factor
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    • "The lack of effective therapeutic options and its high morbidity make DT/AF a challenging disease. The promising results observed with sorafenib suggested that angiogenesis might play an important role in this condition [12]. Although DT/AF is not strictly considered a malignancy, the mechanisms that lead to uncontrolled monoclonal cellular proliferation and survival are similar to those in cancer [13]. "
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    ABSTRACT: Desmoid tumours/aggressive fibromatosis (DT/AF) are infrequent soft-tissue neoplasms. They usually behave as indolent diseases. However, they may grow locally infiltrating or compressing adjacent structures. The role of local treatment is limited and only a few drugs have shown activity.Cases presentation: We report the outcome of two patients affected by progressive DT/AF treated with the angiogenesis inhibitor pazopanib in two different institutions. Both patients achieved dramatic improvement in their symptoms and radiological signs of response. The clinical benefit lasted for more than 1 year and it is still ongoing. Pazopanib is an active treatment in DT/AF. It is the first time this has been reported.
    11/2013; 3(1):13. DOI:10.1186/2045-3329-3-13
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    • "Therefore. new treatment protocols for IAF are gradually being recommended, such as imatinib [41], sunitinib [42], bevacizumab [43], or sorafenib [44]. However, the two cases reported had been treated with imatinib at a dose of 400 mg for liver metastatic GIST. "
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    ABSTRACT: Intra-abdominal fibromatosis (IAF) commonly develops in patients who had abdominal surgery. In rare instances, it occurs subsequent to gastrointestinal stromal tumor (GIST). This special situation has clinical significance in imatinib era. About 1000 patients with GIST in our institution from 1993 to 2010 were re-evaluated based on their clinical and pathological data, the treatment strategies and the follow-up information. We identified 2 patients who developed IAF after GIST resection. Patient 1 was a 54 year-old male and had 5 cm × 4.5 cm × 3.5 cm jejunal GIST excised on February 22, 1994. Three years later, an abdominal mass with 7 cm × 6 cm × 3 cm was identified. He was diagnosed as recurrent GIST from clinical point of view. After excision, the second tumor was confirmed to be IAF. Patient 2 was a 45-year-old male and had 6 cm × 4 cm × 3 cm duodenal GIST excised on August 19, 2008. One year later, a 4 cm mass was found at the original surgical site. The patient refused to take imatinib until the tumor increased to 8 cm six months later. The tumor continued to increase after 6 months’ imatinib therapy, decision of surgical resection was made by multidisciplinary team. The second tumor was confirmed to be IAF with size of 17 cm × 13 cm × 11 cm. Although IAF subsequent to GIST is very rare, it is of clinical significance in imatinib era as an influencing factor for making clinical decision. Virtual slides The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 07/2013; 8(1):125. DOI:10.1186/1746-1596-8-125 · 2.60 Impact Factor
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