Vandana
Dept of Radiotherapy,
CSMMU, Lucknow
Identified in 1921 by James Ewing
2nd most common bone tumor in children
Ewings Sarcoma Family of tumors:
Ewings sarcoma (Bone 87%)
Extraosseous Ewings sarcoma (8%)
Peripheral PNET(5%)
Askins tumor
2
Epidemiology
2% of cancer childhood malignancy
Occurs most commonly in 2nd decade
80% occur between ages 5 and 25
M:F 1.3:1 < 10 yrs
1.6:1 > 10 yrs
Rare in African-Americans and Asians
One of many small round
blue cell tumors seen in
pediatrics
Poorly differentiated tumor
Unknown origin, Thought to
be of neural crest
progenitor cells origin
Consistent cytogenetic abnormality, t(11;22)(q24;q12) present in
90-95%
resultant fusion gene is EWS/FLI-1
Also seen:
t(21;22)(q22;q12) 5-10%
EWS/ERG
t(7;22) and t(17;22) the remainder
EWS/ETV1 and EWS/E1AF respectively
t(1;16)(q21;q13)
present along with t(11;22)
The c-myc protooncogene is frequently expressed in Ewings.
CD 99 ( MIC2)
PAS +ve
1
Pain & swelling of affected area
Scapula (3.8%)
extremities (53%)
direct extension into adjacent bone or soft tissue.
Metastases generally spread through bloodstream
25% present with metastatic disease
Lungs (38%)
Bone (31%)
Bone Marrow (11%)
Nearly all pts. have micromets at diagnosis, so all Need chemo.
Lung 13%
Bone/BM 7 %
Lu+Bone/BM 4 %
Other 1 %
No mets
75%
No uniform staging system.
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Effective local and systemic chemotherapy necessary for
cure.
Induction chemotherapy preferred over starting the
systemic and local therapy
Advantage of this approach:
Evaluation of effectiveness of the regimen
Decreases the vol. of local therapy for surgery or RT
Some bone healing occurs during CT, diminish the risk of
pathological fracture
Local Control Maintenance
Induction Surgery Chemotherapy
Chemotherapy Radiotherapy
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All patients require chemotherapy
Induction chemotherapy
Maintenance chemotherapy
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First Line therapy:
VAC/IE
Vincristine 2.0 mg/m2 on D1
Adriamycin 75 mg/m2 on D1
Cyclophosphamide 1.2 gm/m2 on D1
Ifosphamide 1.8 gm/m2 on D1-5
Etoposide 100 mg/m2 on D1-5
**Substitute adriamycin with dactinomycin (1.2 mg/m2 on D1) after 375
mg/m2
VAI (Vincristine, Adriamycin, Ifosphamide)
VIDE ( Vincristine, ifosphamide, Doxorubicin, Etoposide)
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Cyclophosphamide (250 mg/m2)and topotecan(0.75
mg/m2) D1-D5
Temozolomide and irinotecan
Ifosfamide and etoposide
Ifosfamide ,etoposide and carboplatin
Docetaxel and gemcitabine
IESS-1and IESS-2 showed 4 drug regimen VACD is superior to 3 drug
VAC in terms of RFS and OS.
INT-OO91:Adding IE improved 5-year OS (6172%) for localized
disease, but not for metastatic disease (25%).
Induction Multiagent chemotherapy for at least 12-24
weeks prior to local therapy.
Maintenance (adjuvant chemotherapy) with or without
Radiotherapy is recommended following local control
treatment and the duration of chemotherapy should be
between 28-49 weeks.
35
Surgical Indications
Expendable bone (fibula, rib, clavicle)
Bone defect able to be reconstructed with modest loss of function
May consider amputation if considerable growth remaining
After pre-op RT
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radiation responsive tumor.
**ESMO clinical practice Guidelines for diagnosis, treatment and follow-up for Bone sarcomas. Ref. Annals of
Oncology 21 (Supplement 5) 13,2010
Patient may be treated in supine ,prone, or lateral
position site dependent.
6MV of energy used
For limb, opposing fields normally used.
Tailored portals for every patient.
Field should not cross joints unless essential.
Entire Medullary cavity need not be included in the RT
portal.
Try and spare a strip(1-2cm) of normal tissue for lymph
drainage.
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FIG. Changes in treatment volume. (A) Field
encompassing the entire length of the medullary cavity
for a tumor involving the proximal left humerus. (B)
Tailored field encompassing only the proximal aspect of
the leg for a limited tumor of the left tibia.
Definitive Radiation Therapy:
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Pre-operative Radiation Therapy
Indicated when narrow resection margins are expected
Principle :
To sterilize the tumor compartment before surgery & to
potentially reduce the risk of dissemination during surgery
Local recurrence with pre-op RT
<5%
EI-CESS-92 : Schuck et al IJROBP-1998 & 2003
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Post-operative Radiation Therapy
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Definitive RT
Phase 1:
Gross tumor in bone and soft tissue (pre chemo ) + 2-4 cm longitudinal
margins + 2 cm lateral margins.
Dose:45 Gy/180cGy/#
Boost phase :
Reduced 1-2 cm margins(bone and residual tissue)
Up to total dose of 55.8Gy.
Note: - In case of no soft tissue involvement, the proximal and distal margins in bone are not
changed.
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Figure: Schematic depiction of
GTV1 (pre-induction bone and pre-
induction soft tissue extent) and
GTV2 (pre-induction and post-
induction soft tissue extent)
Dose:
MICROSCOPIC DISEASE- 45 Gy
MACROSCOPIC RESIDUAL 55.8Gy
Pre op RT
45 Gy to original bone and soft tissue
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For rib primary ,with pleural effusion, RT to hemithorax
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Clinical Situation Total Dose (%) Dose per Fraction (%)
Gross disease (after biopsy
only or intralesional
resection)
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If disease extension into pre-formed body cavities e.g. lung &
pelvis, radiotherapy volume includes post induction volume with
2cm margin in order to reduce treatment related toxicity.
Every 2- 3 months
Increase interval after 24 months
Annually after 5 years indefinitely
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30-40% of patients develop relapse with <20%
survival
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Functional results : Of all the patients treated with RT
60 % have good functional activity
20 % have mild morbidities
20 % have significant morbidities
Risk for Post treatment Fractures
Lymphedema
Dermatitis; recall reaction may occur with doxo,
dactinomycin.
Adriamycin cardiomyopathy.
Ifosphamide renal toxicity.
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Second malignancy after RT
Cumulative risk at 15yrs = 6 6.7%
( CESS-81 & CESS-86; IJROBP:1997; 39)
No secondary sarcomas seen at doses <48 Gy
( Kutterch et al; JCO:1996, 14 )
Risk increased by anthracycline and alkylating agent
chemotherapy
Osteosarcoma most common.
Leukemia can also occur.
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Use of 3D-CRT / IMRT as a standard protocol
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Second most common childhood bone tumor.
Small round cell tumor with CD99 (MIC2), PAS positive
Lytic lesion with onion peel appearance on X-Ray
Overall survival with localized disease (55%) and metastatic
disease 22%
Multimodal treatment approach
Induction Chemotherapy for 3-6 cycles and another 6-10
cycles for maintenance.
Surgery when feasible first choice of local therapy
Radiation responsive tumor
There are no randomized trials that have directely
compared Radiotherapy to surgery for local control of
Ewings sarcoma.