Treatment of Ewing Sarcoma

The treatment for Ewings sarcoma is a multidisciplinary approach that focuses on three
treatment modalities namely, chemotherapy, surgery and radiotherapy.
Chemotherapy for the control of micro metastasis; surgery for the local control where
possible; and radiotherapy for the local control where surgery wasnt able or incompletely
controlled.

General Management
o Effective local and systemic chemotherapy is necessary for cure.
o Induction chemotherapy is preferred over starting the systemic and local therapy.
o Advantage of this approach:
Evaluation of the effectiveness of the regimen
Decreases the volume of local therapy for surgery or radiotherapy (RT)
And some bone healing occurs during chemotherapy (CT) Thereby
diminishing the risk of pathological fracture
Chemotherapy
o All patients require to undergo chemotherapy:
Induction chemotherapy
Maintenance chemotherapy
o Effective chemotherapy has improved local control rates achieve with radiation to
85-90%.
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First Line Therapy:

VAC/IE
Vincristine
Adriamycin
Cyclophosphamide
Ifosphamide
Etoposide
*Substitute Adriamycin with Dactinomycin (1.2mg/m2 on D1) after
375mg/m2

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VAI (Vincristine, Adriamycin, Ifosphamide)

VIDE (Vincristine, Ifosphamide, Doxorubicin, Etoposide)

Second Line Therapy: (Relapse and Refractory Disease)

o Cyclophosphamide (250mg/m2) and Topotecan (0.75mg/m2) D1-D5
o Temozolomide and Irinotecan
o Ifosfamide and Etoposide
o Ifosfamide, Etoposide, and Carboplatin
o Docetaxel and Gemcitabine
According to the NCCN guidelines,
Induction of multiagent chemotherapy for atleast 12-24 weeks prior to
local therapy.
Maintenance (adjuvant chemotherapy) is recommended following local
control treatment and the duration of chemotherapy should be between
28-49 weeks.

Surgery
o Preferred for potentially resectable lesions and for those arising in dispensable
bones (e.g. fibula, ribs, small lesions of the hands or feet) for the following
reasons:
Avoids risk of secondary radiation-induced sarcomas.
Analysis of the degree of necrosis in the excised tumor can permit
refinements in the estimate of prognosis.
In the skeletally immature child, resection may be associated with less
morbidity than radiation, which can retard bone growth and cause
deformity.
Tumors affecting the long bones of the leg, distal humerus, or ulna can
usually be resected and reconstructed using intercalary techniques
(allografts, autografts, or metallic prostheses) or joint replacement,
depending of the tumor location.
Radiotherapy
o Preferred in patients who:
Lack a function preserving surgical option because of tumor location or
extent
Those who have clearly unresectable primary tumors following induction
chemotherapy
Patients with lesions of the skull, facial bones, or vertebrae are often
candidates for nonsurgical treatment because of the difficulty in achieving
negative margins without substantial functional deficits.
Patients refusing surgery
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Pre-operative Radiation Therapy:

Indicated when narrow resection margins are expected
Principle:
To sterilize the tumor compartment before surgery and to
potentially reduce the risk of dissemination during surgery.

Local recurrence with pre-op RT: <5%

Post-operative Radiation Therapy:

Should begin within 60 days of surgery and is given concurrently with
consolidation chemotherapy
For gross or microscopic positive margin
For marginal resection
For wide-resection with poor histological response to Neo-adjuvant
chemotherapy

Adjuvant radiotherapy:
Recommended if there is residual microscopic or gross disease after
surgery, or inadequate surgical margins.
Adjuvant hemithorax irradiation improves outcomes in patients with
high-risk chest wall primary tumors (close or involved margins, initial
pleural effusion, pleural infiltration, and intraoperative contamination of the
pleural space).

Treatment of Metastatic Disease

Whole lung irradiation following completion of
chemotherapy/metastasectomy

Surveillance
o Physical examination, local and chest imaging:
o Every 2-3 months
o Increase interval after 24 months
o Annually after 5 years indefinitely.
o CBC and other lab studies as indicated
o Consider Bone scan or PET scan
Prognosis of Ewing Sarcoma
Prognosis for Ewing sarcoma will depend upon pretreatment factors and response to
initial therapy factors.
Pretreatment factors:
Site of Tumor

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Tumor size or volume

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Patients with Ewing sarcoma in the distal

extremities have the best prognosis.
Patients with Ewing sarcoma in the proximal
extremities have an intermediate prognosis,
followed by patients with central or pelvic sites.
Tumor size or volume has been shown to be an
important prognostic factor in most studies.
Cutoffs of a volume of 100 mL or 200 mL and/or
single dimension greater than 8 cm are used to
define larger tumors.

Larger tumors tend to occur in unfavorable sites.

Age

Infants and younger patients have a better

prognosis than do patients aged 15 years and
older.

Gender

Females with Ewing sarcoma have a better

prognosis than males with Ewing sarcoma.

Serum LDH

Increased serum LDH levels before treatment are

associated with inferior prognosis.
Increased LDH levels are also correlated with large
primary tumors and metastatic disease.

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Metastases

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Response to CT

Any metastatic disease defined by standard

imaging techniques or bone marrow
aspirate/biopsy by morphology is an adverse
prognostic factor.
The presence or absence of metastatic disease is
the single most powerful predictor of outcome.
Metastases at diagnosis are detected in about 25%
of patients.
Patients with metastatic disease confined to the
lung have a better prognosis than do patients with
extrapulmonary metastatic sites.
Patients with metastasis to only bone seem to
have a better outcome than do patients with
metastases to both bone and lung.
Better prognosis is seen in patients who are
responsive to chemotherapy

Response to initial therapy factors:

Multiple studies have shown that patients with minimal or no residual viable
tumor after presurgical chemotherapy have significantly better event-free survival (EFS)
than do patients with larger amounts of viable tumor.
Female gender and younger age predict a good histologic response to
preoperative therapy.
For patients who receive preinduction- and postinduction-chemotherapy PET
scans, decreased PET uptake after chemotherapy correlated with good histologic
response and better outcome.
Patients with poor response to presurgical chemotherapy have an increased risk
for local recurrence
Relapse

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30-40% of patients develop relapse with <20% survival.

Early relapse occurs less than 2 years
Consider changing chemotherapy regimen
Late relapse occurs more than 2 years
Continue the previously used chemotherapy