AUTHOR INFORMATION

Section 1 of 11

Authored by Jeffrey A Toretsky, MD, Associate Professor, Departments of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine

Edited by Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center; David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville; and Robert J Arceci, MD, PhD, King Fahd Professor, Division of Pediatric Oncology, Johns Hopkins University School of Medicine

Author's Email:	Jeffrey A Toretsky, MD
Editor's Email:	Samuel Gross, MD

eMedicine Journal, April 17 2006, VOLUME 7, Number 4

INTRODUCTION

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Background: James Ewing first described Ewing sarcoma in 1921, after observing radiosensitivity in a subgroup of bone tumors. In the early 1980s, Ewing sarcoma and the peripheral primitive neuroectodermal tumor were both found to contain the same reciprocal translocation between chromosomes 11 and 22, t(11;22). Later that decade, similar patterns of biochemical and oncogene expression were observed. These tumors were categorized into the Ewing sarcoma family of tumors (ESFT) based on the combination of the shared translocation and the similar cellular physiology. The ESFT includes Ewing sarcoma, peripheral primitive neuroectodermal tumor, neuroepithelioma, atypical Ewing sarcoma, and Askin tumor (a chest wall tumor). The tumors in the ESFT are treated similarly based on their clinical presentation (eg, metastatic, localized) rather than their histologic subtype.

Pathophysiology: Tumors in the ESFT are thought to derive from cells of the neural crest, possibly postganglionic cholinergic neurons. The exact cell of origin of the ESFT is unknown. ESFT research is ongoing to further characterize the biology of the EWS-FLI1 fusion protein and its role in transformation, cell growth, and chemosensitivity. The focus of most research is the fusion protein generated from the t(11;22).

The t(11;22) or one of a series of related translocations occurs in more than 95% of the ESFT. Some argue that without a translocation, the tumor is not an ESFT. This translocation joins the EWS (Ewing sarcoma) gene located on chromosome 22 to an ETS family gene, FLI1 (friend leukemia insertion) located on chromosome 11, t(11;22). The EWS-FLI1 fusion transcript encodes a 68-kd protein with 2 primary domains. The EWS domain is a potent transcriptional activator, while the FLI1 domain contains a highly conserved ETS DNA-binding domain. The EWS-FLI1 fusion protein thus acts as an aberrant transcription factor. EWS-FLI1 transforms mouse fibroblasts, and this transformation requires both the EWS and FLI1 functional domains to be intact. Thus, the EWS-FLI1 fusion protein is implicated in the pathogenesis of ESFT; however, no data exist regarding the cause of the translocation. Downstream targets that are responsible for EWS-FLI1 transformation are currently under study.

The t(11;22) in any individual patient fuses one of many observed combinations of exons together from EWS and FLI1 to form the fusion message. The most common combination is the EWS exon 7 fused to FLI1 exon 6 (type 1 translocation), which occurs in approximately 50-64% of tumors of the ESFT. Retrospective analyses have shown that patients who have localized tumors with the 7/6 fusion have a 70% 4-year survival rate, whereas patients with the other variants have a 20% 4-year survival rate. This difference may be due, at least in part, to different potencies among the variants in their ability to activate gene transcription.

Frequency:

• In the US: The incidence of ESFT from birth to age 20 years is 2.9 per million population annually. Approximately 10% of patients with ESFT are aged 20-30 years. Cases occurring later in life are infrequent.

Mortality/Morbidity: Survival of patients with ESFT is highly dependent on the initial presentation of the disease. Approximately 80% of patients present with localized disease, whereas 20% present with clinically detectable metastatic disease, most often to the lungs, bone, and bone marrow. The overall survival rate in patients with ESFT is 60%; however, for patients with localized disease, it approaches 70%. Patients with metastatic disease have a long-term survival rate that is less than 25%.

Race: Racial distribution is an enigma. The incidence in whites is at least 9 times higher than that in blacks. This is in contrast to osteosarcoma, which has a relatively equal race distribution. African countries report similar incidence rates, with a paucity of ESFT.

Sex: The incidence of ESFT in females is 2.6 per one million population; the incidence in males is 3.3 per one million population.

Age: ESFT peak in the latter half of the second decade of life. Overall, 27% of cases occur in patients in the first decade of life, 64% occur in patients in the second decade of life, and 9% occur in patients in the third decade of life.

CLINICAL

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History:

• Patients with the Ewing sarcoma family of tumors (ESFT) usually present with pain and often have a palpable mass.



• Patients with long bone lesions can present with a pathologic fracture.



• Back pain may indicate a paraspinal, retroperitoneal, or deep pelvic tumor.



• Systemic symptoms of fever and weight loss can also occur and often indicate metastatic disease.

Physical:

• The ESFT can occur in virtually any location; careful examination of painful sites with inspection and palpation is critical.



• Because patients with ESFT can present with disease close to bone, tumors can result in neuropathic pain. Thus, a comprehensive neurological examination to evaluate asymmetric weakness, numbness, or pain is critical.



• Patients with lung metastases can present with asymmetric breath sounds, pleural signs, or rales.



• Patients with significant bone marrow metastases can present with petechiae or purpura from thrombocytopenia.

Causes:

• No known cause of the ESFT exists.



• Cases are thought to be sporadic; however, family members of patients with ESFT have an increased incidence of neuroectodermal and stomach malignancies.



• The ESFT is rarely reported as a neoplasm occurring following the treatment of another neoplasm (second malignancy).

DIFFERENTIALS

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Neuroblastoma
Non-Hodgkin Lymphoma
Nonrhabdomyosarcoma Soft Tissue Sarcomas
Osteomyelitis
Osteosarcoma
Rhabdomyosarcoma
Rickets

WORKUP

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Lab Studies:

• No pathognomonic or suggestive blood studies can be used to diagnose Ewing sarcoma family of tumors (ESFT). Depending on the patient’s age and presenting symptoms, blood tests, including erythrocyte sedimentation rate, C-reactive protein, blood culture, and complete blood cell count, might be helpful when considering other diagnoses.

Imaging Studies:

• Primary lesion evaluation


• • The priority is to obtain imaging studies of the suspected primary lesion or region with symptoms.
  
  
  
  • If a bony mass is palpated, plain radiography is indicated.
  
  
  
  • MRI of the region can help to identify the extent of disease.
  
  
  
  • CT imaging is helpful to delineate any bony involvement.
  
  
  
  • Tumors that are adjacent to critical neurologic structures require immediate MRI scanning and consideration of emergent radiation therapy, surgery, and steroids to attempt to prevent nerve damage.
  
  
  
• Metastatic evaluation: Metastatic evaluation includes chest CT scanning and radioisotope bone scanning. If a tumor is likely based on initial study results, the chest CT scan is best obtained prior to surgical biopsy to avoid confusion with postoperative atelectasis. Most centers now use either FDG-PET or whole body MRI as a more sensitive indicator of metastatic disease. Neither modality has been proven to improve prognosis, yet a general consensus among investigators suggests that one of the reasons that patients with localized disease recur at distal sites is because of the underdiagnosis of metastatic disease.

Procedures:

• Biopsy


• • If an ESFT or another tumor is probable, consultation with a pediatric oncologist should be sought before any biopsy is obtained.
  
  
  
  • The definitive diagnosis requires a biopsy specimen.
  
  
  
  • The biopsy specimen should be evaluated by routine staining as well as immunohistochemistry using antibodies to differentiate from other small round blue cell tumors such as rhabdomyosarcoma and lymphoma.
  
  
  
  • Cytogenetic studies should be used to confirm the diagnosis if the t(11;22) or a related translocation is found. For standard cytogenetics, fresh tissue should be sent in appropriate media to a laboratory of cytogenetics. In addition, a small piece of tumor should be snap-frozen in liquid nitrogen to permit molecular studies.
  
  
  
  • Biopsies should be obtained with complete consideration of any potential therapy because all patients with ESFT require some form of definitive local management of their disease.
  
  
  
  • Inappropriate biopsy or resection often results in increased patient morbidity or mortality.
  
  
  

TREATMENT

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Medical Care:

• Patients should be treated under the supervision of a pediatric oncologist, and care should be directed by a comprehensive pediatric oncology center.



• Patients must be evaluated and treated by a multidisciplinary team, including pediatric oncologists, radiation oncologists, surgeons, radiologists, pathologists, nurses, social workers, occupational/physical therapists, blood bankers, psychologists, school tutors, and pharmacists.



• In-house expertise from infectious disease specialists is often required.



• The 6- to 9-month treatment consists of alternating courses of the 2 following chemotherapeutic regimens: (1) vincristine, doxorubicin, and cyclophosphamide and (2) ifosfamide and etoposide.



• Management of the primary tumor site is critical to the long-term cure of the patient. Definitive surgical margins are desirable (eg, removal of fibula, limb salvage with extensive margins).



• In the absence of a minimally morbid surgical procedure, achieve local control with radiation therapy. Dose to tumor and fractionation is site-dependent.

Surgical Care: Any surgery should be performed under the supervision of experienced oncologic surgeons specialized in the area of the body where the tumor is found. The specific surgery is highly patient-dependent.

Consultations:

• Orthopedic surgeon


• • Lesions close to bone that are potentially resectable require consultation with an orthopedic oncologist prior to biopsy.
  
  
  
  • Biopsy planning is critical because an inappropriate biopsy could contaminate tissue planes.
  
  
  
• Neurologist: Lesions close to nerve roots, ganglia, or plexuses might result in neurologic symptoms.



• Pathologist: When a mass is resected from a pediatric patient, a pathologist should be aware of the procedure and the differential diagnosis. This is critical for appropriate diagnostic studies to be performed.

Diet:

• All patients require close monitoring of their caloric intake during treatment.



• Dietitian services are often indicated; however, no special diets are required for treatment.

Activity:

• Activity limitations depend on the location of primary and metastatic lesions.



• No general restrictions are indicated.

MEDICATION

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Because the survival rate of patients with ESFT is not satisfactory for those with either localized or metastatic disease at this time, a national cooperative group, the (Children's Oncology Group (COG), which was formed in part by the merger of the former Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG), is pursuing clinical trials not only to improve outcome but also to reduce morbidity. Medical therapy varies slightly among European and North American pediatric oncologists but is similar to that described above under Medical Care. New COG protocols intend to improve on the outcome from recent trials.

Dose intensity is critical in treatment of ESFT. To facilitate maximum dosing of chemotherapeutic agents, anticipatory supportive care is necessary. Neutrophils are stimulated with granulocyte colony-stimulating factor (G-CSF), and fevers are treated aggressively. New symptoms occurring while patients are under treatment should be closely evaluated and monitored.

Drug Category: Antineoplastic agents -- Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2), then finally a mitotic cell division (ie, phase M).

Cell division rate varies for different tumors. Most common cancers increase very slowly in size compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly than malignant ones from chemotherapy and is, in part, the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle–specific, while others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

Drug Name	Doxorubicin (Adriamycin) -- Multiple mechanisms of action exist (eg, DNA intercalation, topoisomerase-mediated DNA strand breaks, oxidative damage via free radical production).
Adult Dose	COG investigational protocols currently in progress, refer to oncologist
Pediatric Dose	COG investigational protocols currently in progress, refer to oncologist
Contraindications	Documented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; preexisting myelosuppression
Interactions	Increased risk of cardiotoxicity when combined with heart irradiation; may decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin
Pregnancy	D - Unsafe in pregnancy
Precautions	Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function; commonly causes nausea, diarrhea, and alopecia

Drug Name	Cyclophosphamide (Cytoxan) -- Exerts its cytotoxic effect by alkylation of DNA, which leads to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
Adult Dose	COG investigational protocols currently in progress, refer to oncologist
Pediatric Dose	COG investigational protocols currently in progress, refer to oncologist
Contraindications	Documented hypersensitivity; severely depressed bone marrow function; severe hemorrhagic cystitis
Interactions	Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution with bone marrow suppression and impaired renal or hepatic function; modification of dosage may be necessary; may cause myelosuppression (ie, leukopenia, hemolytic anemia, thrombocytopenia), alopecia, hemorrhagic cystitis (monitor for hematuria, prehydrate, administer with IV mesna), cardiotoxicity (at high doses), impaired fertility, headache, and darkening of skin and fingernails; moderate-to-high emetogenic potential (based on the dose, causes anorexia, diarrhea, stomatitis, and mucositis)

Drug Name	Vincristine (Oncovin) -- Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin. Inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.
Adult Dose	COG investigational protocols currently in progress, refer to oncologist
Pediatric Dose	COG investigational protocols currently in progress, refer to oncologist
Contraindications	Documented hypersensitivity; IT administration (universally fatal); demyelinating form of Charcot-Marie-Tooth syndrome
Interactions	Asparaginase may decrease vincristine clearance; acute pulmonary reactions may occur with concomitant use of mitomycin C; additive toxicity with other neurotoxic drugs
Pregnancy	D - Unsafe in pregnancy
Precautions	Dosage modification required in patients with impaired hepatic function, patients receiving other neurotoxic drugs, or patients with preexisting neuromuscular disease; avoid extravasation; severe constipation and/or peripheral neuropathy are relative contraindications

Drug Name	Ifosfamide (Ifex) -- Exerts its cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
Adult Dose	COG investigational protocols currently in progress, refer to oncologist
Pediatric Dose	COG investigational protocols currently in progress, refer to oncologist
Contraindications	Documented hypersensitivity; depressed bone marrow function
Interactions	Phenobarbital, phenytoin, chloral hydrate, and other drugs that interfere with cytochrome P-450 activity may alter effects of ifosfamide
Pregnancy	D - Unsafe in pregnancy
Precautions	Hemorrhagic cystitis is the dose-limiting toxicity (monitor for hematuria and administer with IV mesna); myelosuppression, nausea, alopecia, and impaired fertility may occur; possesses moderate emetogenic potential

Drug Name	Etoposide (VePesid) -- Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single- and double-strand DNA breaks.
Adult Dose	COG investigational protocols currently in progress, refer to oncologist
Pediatric Dose	COG investigational protocols currently in progress, refer to oncologist
Contraindications	Documented hypersensitivity; IT administration (may cause death)
Interactions	May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells
Pregnancy	D - Unsafe in pregnancy
Precautions	Known to cause anaphylaxis; dosage reduction with low serum albumin, bone marrow suppression, or renal impairment

Drug Category: Uroprotectants -- Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide or cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.

Drug Name	Mesna (Mesnex) -- Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Adult Dose	Dose dependent on dose of ifosfamide or cyclophosphamide, typically 60-100% of the antineoplastic agent used; may be administered as an initial bolus followed by IV continuous infusion or as intermittent IV infusions prior to and following chemotherapy regimen
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	May increase warfarin affect, adjust dose according to INR target
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor morning urine for hematuria prior to ifosfamide or cyclophosphamide dose; common adverse effects include hypotension, headache, GI toxicity, and limb pain

FOLLOW-UP

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Further Inpatient Care:

• Chemotherapy can be administered on either an inpatient or an outpatient basis, depending on patient tolerance and proximity to the hospital.



• Patients often develop episodes of fever while neutropenic, resulting in 3- to 7-day hospitalizations between cycles of chemotherapy.

Further Outpatient Care:

• Chemotherapy care and follow-up


• • Most patients require red blood cell and platelet support starting approximately 2 months into therapy and continuing through the completion of therapy. While receiving G-CSF for neutrophil support, biweekly blood cell counts are necessary.
  
  
  
  • A full physical examination is required prior to each cycle of chemotherapy and any time suspicious signs or symptoms arise between cycles. Suspicious signs include signs similar to those at the time of presentation as well as unexplained fever or pain.
  
  
  
  • Evaluation of primary and metastatic sites is performed approximately every 10-12 weeks while on therapy and at 3- to 4-month intervals during the first year following the completion of therapy.
  
  
  
  • Reevaluations are spaced out gradually for 5-6 years following the completion of therapy. At that time, no further scanning is indicated; however, the patient should have annual follow-up visits to monitor function of the primary site and late effects of therapy.
  
  
  
• Long-term follow-up


• • Late effects from chemotherapy require regular follow-up by a provider trained to evaluate for long-term sequelae of therapy.
  
  
  
  • Recurrence of primary disease is the major risk in the first 10 years from the time of diagnosis.
  
  
  
  • Second malignancy occurs in approximately 1-2% of patients beginning after 5 years from the time of diagnosis. The most common second malignancy is acute myeloid leukemia.
  
  
  
  • Therapeutic toxicities to the heart and kidneys and the nervous, endocrine, and mental systems need monitoring both in patients who experienced an acute toxicity as well as those acquiring symptoms following the completion of therapy.
  
  
  

Transfer:

• Patient care during chemotherapy is generally under the direct supervision of the pediatric oncologist. The primary care physician should be kept informed regarding patient progress and complications.



• After therapy is completed, the primary physician should become more involved in patient care.

Deterrence/Prevention:

• No known methods to prevent ESFT exist.

Complications:

• Chemotherapy complications


• • Vincristine primarily causes neuropathy, including constipation, myalgias, arthralgias, and cholestasis.
  
  
  
  • Doxorubicin causes myocardial dysfunction and pancytopenia.
  
  
  
  • Cyclophosphamide causes pancytopenia and a dosage-dependent hemorrhagic cystitis.
  
  
  
  • Ifosfamide is similar to cyclophosphamide, although it has a higher incidence of hemorrhagic cystitis, which requires the use of 2-mercaptoethane sulfonate sodium (MESNA). Patients near the end of therapy occasionally develop the Fanconi syndrome of electrolyte wasting.
  
  
  
  • Etoposide can result in pancytopenia as well as anaphylactic reactions and is implicated in the development of second malignancies, particularly acute myelogenous leukemia.

  • The combination of chemotherapy in general results in alopecia, nausea, vomiting, and occasionally diarrhea. The nutritional and psychologic statuses of patients undergoing this therapy must be monitored closely.
  
  
  
• Surgical complications


• • Surgical complications generally include infection and bleeding.

  • Specific complications relate to the site of surgery and the overall condition of the patient at the time of surgery.
  
  
  
• Radiation complications


• • Radiation therapy complications are a direct result of the sites of radiation.

  • Patients who receive large pelvic doses of radiation often have increased problems with pancytopenia, malnutrition, and diarrhea.

  • Radiation increases the likelihood of second malignancies, particularly in the radiation field.
  
  
  

Prognosis:

• At this time, the only significant factor that determines prognosis is the presence or absence of metastatic disease.

Patient Education:

• Any patient, and their family, diagnosed with a malignancy needs significant education. For the patient, this includes age and developmentally appropriate information about their disease and therapy. This includes knowledge of the specific disease and prognosis. It also includes information about expected complications, particularly fever management.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Chemotherapy involves a group of medications with clear and significant risks, both immediate and long-term. Obtaining informed consent is required prior to beginning therapy if the patient will be enrolled in a clinical trial. If no appropriate trial is accruing patients, then the oncologist refers to the most recent clinical trial to determine the best possible therapeutic regimen. A consent form that includes the recommended agents and their side effects should be strongly considered in these circumstances.

Special Concerns:

• Because the ESFT is rare, ESFT is often not considered in a differential diagnosis until a biopsy reveals a small round blue cell tumor. Usually, malignancy is in the differential diagnosis prior to a biopsy, and, for this reason, consultation with a pediatric oncologist is critical. The ESFT should be considered in the differential diagnosis in a patient in the second or third decade of life with a soft tissue or bony mass that causes the physician to consider a neoplasm.

TEST QUESTIONS

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CME Question 1: Which of the following is the most diagnostic blood test to identify Ewing sarcoma family of tumors (ESFT) in a patient who presents with a femur mass?

A: Sedimentation rate
B: Alpha-fetoprotein
C: Lactate dehydrogenase (LDH)
D: None of the above
E: All of the above

The correct answer is D: Because tumors of the ESFT are diagnosed by histologic findings, no specific blood tests are available. A test of sedimentation rate can provide information about possible infection.

CME Question 2: An 18-year-old woman presents with a 2-week history of fever, pallor, and fatigue. She completed therapy for a tumor of the Ewing sarcoma family of tumors (ESFT) of the rib 2 years ago. Which of the following should be included in her differential diagnosis?

A: Mononucleosis
B: Recurrent ESFT
C: Acute myeloid leukemia
D: All of the above
E: None of the above

The correct answer is D: Patients treated with chemotherapy can develop second malignancy, which should be considered in addition to the differential diagnoses for any given clinical scenario.

Pearl Question 1 (T/F): The Ewing sarcoma family of tumors (ESFT) can occur anywhere in the body.

The correct answer is True: The ESFT can occur in virtually any location; careful examination of painful sites with inspection and palpation is critical.

Pearl Question 2 (T/F): Siblings of a patient with a femur tumor in the Ewing sarcoma family of tumors (ESFT) have increased likelihood of developing the disease.

The correct answer is False: No evidence exists to support increased risk of ESFT in siblings of an affected patient.

Pearl Question 3 (T/F): A patient being treated for a pelvic tumor in the Ewing sarcoma family of tumors (ESFT) is 5 months into a clinical trial. He demonstrated a significant partial response at the most recent MRI reevaluation 3 weeks ago. The patient reports sudden shooting pains down the left leg with some calf numbness; however, this is a normal response to therapy and no treatment is necessary.

The correct answer is False: An MRI of the pelvis is necessary. Neurologic symptoms can indicate nerve involvement with ESFT, which is considered an oncologic emergency requiring immediate radiation therapy.

Pearl Question 4 (T/F): The 3 characteristics shared by Ewing sarcoma and peripheral primitive ectodermal tumors are oncogene expression, biochemical characteristics, and translocation (often between chromosomes 11 and 22).

The correct answer is True: Peripheral primitive ectodermal tumors are considered part of the Ewing sarcoma family of tumors (ESFT) because of similar oncogene expression, biochemical characteristics, and translocation (often between chromosomes 11 and 22).

BIBLIOGRAPHY

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• Grier HE, Krailo MD, Tarbell NJ, et al: Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003 Feb 20; 348(8): 694-701[Medline].
• Gurney JG, Swensen AR, Bulterys M: Malignant Bone Tumors. SEER 1999; 99-110.
• Meyers PA, Krailo MD, Ladanyi M, et al: High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis. J Clin Oncol 2001 Jun 1; 19(11): 2812-20[Medline].
• Miser JS, Krailo MD, Tarbell NJ, et al: Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study. J Clin Oncol 2004 Jul 15; 22(14): 2873-6[Medline].
• Paulussen M, Ahrens S, Dunst J, et al: Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86. J Clin Oncol 2001 Mar 15; 19(6): 1818-29[Medline].
• Saylors RL, Stine KC, Sullivan J, et al: Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol 2001 Aug 1; 19(15): 3463-9[Medline].
• Uren A, Toretsky JA: Ewing's Sarcoma Oncoprotein EWS-FLI1: the Perfect Target without a Therapeutic Agent. Future Onc, 1: 521-528, 2005.

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