Desmoid-type fibromatosis: toward a holistic management.

PURPOSE OF REVIEW: Desmoid-type fibromatosis, a rare locally aggressive fibroblastic proliferation, is a treatment challenge. This review aimed to explore recent data about the management of desmoid-type fibromatosis. RECENT FINDINGS: New data underline the role of kinases and ɣ-secretase in stimulating cell proliferation and invasiveness in desmoid-type fibromatosis. This explains the proven activity of multikinase inhibitors (sorafenib or pazopanib) in the management of desmoid-type fibromatosis or the emerging role of a ɣ-secretase inhibitor. An international guideline for management was recently published, and this guideline take into account patient point of view. Lastly, recent studies highlight the multidimensional burden of desmoid-type fibromatosis, particularly health-related quality of life (HRQoL). SUMMARY: Active surveillance with planned MRI is the first-line management in desmoid-type fibromatosis. A site-specific and stepwise approach should be considered for progressive desmoid-type fibromatosis. Further, a risk-benefit analysis that considers the side effects and long-term sequelae should be conducted before deciding to start any treatment. A less aggressive approach should be considered. Multikinase inhibitors are effective, but their tolerability and side effects should be discussed with the patients. The symptoms and HRQoL should be integrated in decision-making. Desmoid-type fibromatosis patients should be offered support to address their needs supportive care.

Surgical management and minimally invasive approaches for the treatment of metastatic sarcoma.

Soft tissue sarcomas describe a very heterogeneous group of soft tissue tumors mainly arising in the lower extremities. If diagnosed at an early stage and a complete resection of the primary tumor is achieved, the patients' prognosis is excellent. However, metastatic tumor spread is common with only limited treatment possibilities. Despite an improved insight into tumor biology of sarcomas, no notable improvement has been gained in the last 20 years regarding prognosis of patients. Metastatic lung disease has long been the preserve of systemic treatments, local treatments being considered in a purely palliative intention. Several studies have objectified benefit to the local treatment of metastases, especially in an oligometastatic state. The development of techniques for stereotactic radiotherapy on the one hand and the refusal or contraindication for surgery on the other hand inaugurated studies in this direction. Besides surgery and radiotherapy, other local modalities have been investigated in the last few years such as thermal therapy (radiofrequency and laser ablation) or combined modalities (isolated limb perfusion and deep-wave hyperthermia plus chemotherapy) to help patients with metastatic soft tissue sarcoma. Minimally invasive, image-guided therapies such as thermal ablation should be considered particularly in patients who are not suitable surgical candidates or may have exhausted all other viable surgical options. Some of these techniques will be reviewed in this article, and their value for the patients will be evaluated in the light of indication from tumor biology and technical feasibility. These highly selected and specific procedures should only be performed after decision making in an interdisciplinary sarcoma-board.

Palifosfamide, a bifunctional alkylator for the treatment of sarcomas.

Ifosfamide is a chemotherapeutic prodrug used in the treatment of several tumor entities, including bone and soft-tissue sarcoma. However, the application of high-dose ifosfamide is not feasible because of severe side effects caused by metabolites. The active metabolite isophosphoramide mustard is not suitable for administration because of chemical instability. ZIOPHARM Oncology Inc, under license from Dekk-Tec Inc, is developing palifosfamide, a formulation of isophosphoramide mustard with tris(hydroxymethyl)aminomethane salt-stabilization (palifosfamide-tris) and previously with lysine-stabilization (palifosfamide-lys). Preclinical studies and phase I and I/II clinical trials demonstrated that palifosfamide-tris had an antitumor efficiency comparable or superior to that of ifosfamide. Patients treated with palifosfamide-tris did not display any of the neurotoxic or nephrotoxic side effects associated with ifosfamide. At the time of publication, data from phase II trials were being evaluated and phase III trials were being planned. palifosfamide-tris is expected to be a safer and less toxic alternative to ifosfamide; however, considering other new approaches under investigation for tumors such as sarcoma, such as molecular-based treatment strategies, it is unclear what position palifosfamide-tris might occupy on the market.

Prophylactic treatment of known ifosfamide-induced encephalopathy for chemotherapy with high-dose ifosfamide?

We report about a case of advanced Ewing sarcoma in a 30-year-old woman. Initial treatment was started according to the Euro-Ewing 99 protocol. During the initial therapy, an ifosfamide-induced encephalopathy occurred as status epilepticus. Because of cerebral toxicity, the following chemotherapies went without ifosfamide. During final radiotherapy multiple lung metastasis were diagnosed. After two cycles of chemotherapy with cyclophosphamide and topotecan (no response), left thoracotomy, and palliative pneumectomy, the patient was transferred to our ward for further treatment. Undergoing two cycles of chemotherapy with ifosfamide 4 g/m(2) intravenously for 3 consecutive days followed by high-dose chemotherapy (HDCT) according to the ICE-regimen (ifosfamide 2 g/m(2), carboplatin 200 mg/m(2), and etoposide 2 x 100 mg/m(2) intravenously for 6 consecutive days), and peripheral blood stem cell transplantation (PBSCT), complete remission was achieved. Under preventive therapy with methylene blue, thiamin, and glucose 5% infusions, no encephalopathy occurred.