X-Ray of a child with Ewing's sarcoma of the tibia
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Ewing's Sarcoma

Ewing's sarcoma is the common name for primitive neuroectodermal tumor. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, and the ribs. James Ewing (1866-1943) first described the tumor, establishing that the disease was separate from lymphoma and other types of cancer known at that time. Ewing's sarcoma occurs most frequently in teenagers. Ewing's sarcoma is the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11. more...

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Clinical Findings

Ewing's sarcoma usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age, although it can occur in younger children and older adults. It can occur anywhere in the body, but most commonly in the pelvis and proximal long tubular bones. The metaphysis and diaphysis of the femur are the most common sites, followed by the tibia and the humerus. Thirty percent are overtly metastatic at presentation.

The most common clinical findings are pain and swelling.

Imaging Findings

On conventional radiographs, the most common osseous presentation is a permeative lytic lesion with periosteal reaction. The classic description of lamellated or "onion skin" type periosteal reaction is often associated with this lesion. Plain films add valuable information in the initial evaluation or screening. The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differention of benign versus aggressive or malignant lytic lesions.

MRI should be routinely used in the work-up of malignant tumors. MRI will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels). Gadolinium contrast is not necessary as it does not give additional information over noncontrast studies, though some current researchers argue that dynamic, contrast enhanced MRI may help determine the amount of necrosis within the tumor, thus help in determining response to treatment prior to surgery.

CT can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs and pelvis. Both CT and MRI can be used to follow response to radiation and/or chemotherapy.

Bone scintigraphy can also be used to follow tumor response to therapy.

Differential Diagnosis

Other entities that may have a similar radiologic presentation include osteomyelitis, osteosarcoma (especially telangiectatic osteosarcoma) and eosinophilic granuloma. Soft tissue neoplasms such as malignant fibrous histiocytoma that erode into adjacent bone may also have a similar appearance.

Treatment

Because almost all patients with apparently localized disease at diagnosis have occult metastatic disease, multidrug chemotherapy as well as local disease control with surgery and/or radiation is indicated in the treatment of all patients (2). Treatment often consists of adjuvant chemotherapy generally followed by wide or radical excision, and may also include radiotherapy. Complete excision at the time of biopsy may be performed if malignancy is confirmed at that time.

Prognosis

Staging attempts to distinguish patients with localized from those with metastatic disease. Most commonly, metastases occur in the chest, bone and/or bone marrow. Less common sites include the central nervous system and lymph nodes.

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A phase II randomized study evaluating the safety and efficacy of ABT-510 in subjects with locally advanced or metastatic soft tissue sarcoma - Clinical
From Journal of Drugs in Dermatology, 8/1/03

Sponsored by: Abbott Laboratories

Purpose: The primary objective of this study is to assess the safety and effectiveness of ABT-510 in subjects with locally advanced or metastatic soft tissue sarcoma.

Study Type: Interventional

Study Design: Treatment

Ages eligible for study: 18 years and above, both genders

Inclusion Criteria:

* The subject is at least 18 years of age.

* The subject has histologically confirmed high grade locally advanced or metastatic soft tissue sarcoma (excluding Ewing's sarcoma and chondrosarcoma) not amenable to surgery, radiotherapy or combined modality therapy with curative intent.

* The subject must have at least one lesion with measurable disease by RECIST criteria using CT or MRI.

* The subject has received no more than two cytotoxic treatment regimens, not including adjuvant therapy for sarcoma.

* The subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.

* The subject is able to self-administer or has a caregiver who can reliably administer subcutaneous injections.

* The subject must have adequate bone marrow, renal and hepatic function as follows: *Bone marrow: White blood cell count (WBC) greater than or equal to 3,000/[mm.sup.3]; * Platelets; greater than or equal to 100,000/[mm.sup.3]; * Hemoglobin greater than or equal to 9.0 g/dL; * Renal function: Serum creatinine less than or equal to 2.0 mg/dL; * Hepatic function: Bilirubin less than or equal to 1.5 mg/dL; AST and ALT less than or equal to 1.5 X the upper normal limit (ULN) unless liver metastases are present, then AST and ALT less than or equal to 5.0 x ULN.

* The subject must not be pregnant or lactating and all subjects (male and female) must use a contraceptive method deemed acceptable by the investigator while in the study and for up to two months following completion of therapy.

* The subject has voluntarily signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent prior to any study specific procedures.

Exclusion Criteria:

* The subject has known Central Nervous System (CNS) metastasis. Brain CT or MRI within 28 days of enrollment is required to confirm absence of CNS metastases. Subjects with previously treated brain metastases are eligible if no evidence of disease is observed on CT.

* The subject has received any therapy for sarcoma including chemotherapy, radiotherapy or any investigational therapy administration.

* The subject exhibits evidence of clinically significant uncontrolled condition(s) and/or is considered by the investigator to be unable to tolerate the proposed treatment or procedures.

* The subject exhibits evidence of clinically significant uncontrolled condition(s) and/or is considered by the investigator to be unable to tolerate the proposed treatment or procedures.

* Subject has history of other previous malignancies within five years, with the exception of: * Adequately treated in situ carcinoma of the cervix uteri; * Basal or squamous cell carcinoma of the skin.

* The subject's life expectancy is less than 12 weeks.

Location and Contact Information

Ray Knight, BS MBA Tel: 847-938-1378 E-mail: raymond.knight@abbott.com

Michigan

Study ID Numbers M02-534

NLM Identifier NCT00061659

COPYRIGHT 2003 Journal of Drugs in Dermatology
COPYRIGHT 2003 Gale Group

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