ROLE OF RADIOTHERAPY IN EWINGS SARCOMA

1. EWINGS SARCOMA: ROLE OF
RADIOTHERAPY
DR.PAUL GEORGE
RCC

3. Introduction
• Identified in 1921 by James Ewing
• 2nd most common bone tumor in children
• Ewing’s Sarcoma Family of tumors:
–
–
–
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Ewing’s sarcoma (Bone –87%)
Extraosseous Ewing’s sarcoma (8%)
Peripheral PNET(5%)
Askin’s tumor
Occurs most commonly in 2nd decade
◦ 80% occur between ages 5 and 25
3

4. characteristics
• Small blue round cell neoplasm
• Consistent cytogenetic abnormality
t(11;22)(q24;q12) in 90-95%
resultant fusion gene is EWS/FLI-1
• The c-myc protooncogene is
frequently expressed in Ewing’s.
• CD 99 ( MIC2)
• PAS +ve
• more common in diaphysis or metadiaphysis
central axis (47%): pelvis25%, chest wall, spine,H&N
extremities (53%)
• 25% present with metastatic disease
– Lungs (38%)Bone (31%)Bone Marrow (11%)
• Nearly all pts. have micromets at diagnosis ,so all Need chemo.

7. GENERAL PRINCIPLES OF
MANAGEMENT
Induction
Chemotherapy
12 TO 24WKS
VAC/IE
Local Control
Maintenance
• Surgery
• Radiotherapy
• Chemotherapy
AT
12WK/18WK
UP TO 1YEAR

8. LOCAL THERAPY
The need to attain complete tumor eradication
must be weighed against the twin goals of
• maximizing function and
• minimizing long-term morbidity

9. RT versus surgery
• No randomized trials which directly compare both
modalities, and their relative roles continue to be debated
• Contemporary treatment guidelines emphasize surgical
resection as the local control modality of choice
• In many retrospective series, rates of local control and survival
are superior after surgery compared to RT
alone.However, larger cooperative group studies have failed
to reflect this advantage, and selection bias likely accounts for
at least some of these results.

10. • CESS-86, which included central quality assurance, the fiveyear RFS rates following chemotherapy plus either RT or
surgery were 67 and 65 percent, respectively
• US Intergroup study 0091 (IESS III), a randomized comparison
of VACA +/- IE,The rates of five-year, event-free survival (EFS)
and local failure in the entire group were 49 and 21 percent,
respectively which was present regardless of the local control
modality.
The choice between surgery and RT is dictated by
• the age of the patient,
• the location and size of the primary, and
• functional as well as long-term consequences of therapy.

11. SURGERY
Surgery is preferred for potentially resectable lesions,
and for those arising in dispensable bones (eg, fibula, rib,
small lesions of the hands or feet) for the following
reasons:
• It avoids the risk of secondary radiation-induced
sarcomas.
• An 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

12. • 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 on tumor
location

13. RADIOTHERAPY & EWINGS
MELTING LIKE SNOW
1.Control of PRIMARY
2.ADJUANT/POSTOP RT
3.METASTATIC SETTING

14. RT FOR LOCAL CONTROL OF THE PRIMARY
Patients who
• lack a function-preserving surgical option because of tumor
location or extent, and
• those who have clearly unresectable primary tumors following
induction chemotherapy are appropriate candidates for RT.
Primary tumors involving the proximal humerus and upper
Scapula may be best treated with RT, since limb reconstruction is
difficult and shoulder morbidity may be substantial.
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 deficit

15. Adjuvant RT
• Recommended if there is residual microscopic or gross
disease after surgery, or inadequate surgical margins
• For bulky tumors in difficult sites such as the pelvis,
combined surgery and RT might allow for a more limited
surgical procedure, better functional outcome, and
enhanced local control as compared to single modality
therapy.
• Prophylactic whole lung irradiation is not recommended
(IESS1)
• 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)

16. RT FOR METASTATIC DISEASE
1.Management of primary site
2.Pulmonary metastasis
3.Bone & soft tissue mets
4.Total Body Irradiation?

17. Management of the primary site:
• difficult to justify a large resection of the
primary site because of the poor long-term
prognosis.On the other hand, RT can provide
adequate local control with acceptable
morbidity

18. Pulmonary metastases: In highly selected patients, between 20 and 40
percent five-year OS can be achieved
In the CESS and EICESS trials, the rate of pulmonary relapse was
reduced by 50 percent over that for patients who did not undergo
lung RT, and this was accompanied by improvements in event free
survival (from 19 to 40)
Despite the lack of controlled trials, low-dose bilateral lung irradiation
(15 to 18 Gy, in daily 1.5 to 2.0 Gy fractions) with a focal boost dose
to a total of 40 to 50 Gy to large deposits is commonly
recommended for patients with pulmonary metastases who have
had a good response to chemotherapy

19. Bone and soft tissue metastases limited data
For patients with solitary or limited bone metastases, RT is
delivered to metastatic lesions (doses of 40 to 50 Gy) in addition to
irradiation of the primary tumor for patients who are good
responders of chemotherapy.

20. TOTAL BODY IRRADIATION
TBI has not contributed significantly to the
control of metastatic disease. This approach
should not be considered at present
TBI: The use of TBI as a conditioning regimen
prior to high-dose chemotherapy and
hematopoietic stem cell transplantation for
patients with poor-risk disease

21. RADIATION TREATMENT PLANNING —
• Treatment volume — Historically, Ewing sarcoma was
thought to be a tumor of the bone marrow.
Consequently, RT was administered to the entire
marrow cavity of the involved bone.
• However, an analysis of the RT fields for the Intergroup
Ewing's Sarcoma Study Group (IESS) trial I suggested
that most relapses were at the site of initially bulky
tumor. Subsequent efforts were geared toward
reducing the irradiated field and targeting higher doses
to the site of the initial primary tumor.

22. In 1983, the Pediatric Oncology Group attempted a randomized
trial of whole bone versus tailored-field RT after 12 weeks of
induction chemotherapy .
IESS III: first cooperative group trial to include tailored RT
ports, and the first to be carried out with modern MRI
imaging of the primary site and CT-based treatment planning.
The addition of IE significantly improved five-year survival (72
versus 61 percent) and event-free survival rates (69 versus 54
percent), which was present regardless of the local control
modality.

24. 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.

25. PLANNING CONT…
DEFINITIVE RT:
Phase 1:
• Gross tumor in bone and soft
tissue (pre chemo ) + 2cm
longitudinal margins + 2 cm lateral
margins
• Dose:45 Gy/180-225cGy/#
Boost phase :
• Reduced 1-2 cm margins
(bone and residual tissue)
Up to total dose of 55.8Gy(10.8Gy/6#)

26. • For rib primary ,with pleural effusion, RT to hemithorax
• Lesion of vertebral body treated with 45Gy.
Adjuant RT
• Pretreatment gross tumor volume +surgical scar+2cm
margin(45 Gy) boost to post op residual +2cm margin.
Dose:
• MICROSCOPIC DISEASE- 45 Gy
• MACROSCOPIC RESIDUAL – 55.8Gy
Pre op RT
• 45 Gy to original bone and soft tissue

27. METASTATIC LESIONS
• For isolated pulmonary metastasis: low-dose bilateral lung
irradiation (15 to 18 Gy, in daily 1.5 to 2.0 Gy fractions)
• Pain palliation– advanced disease.
• Isolated bone secondaries

28. Attention to potential RT effects on normal tissue is critical in
radiation planning
• Even partial treatment of uninvolved epiphyseal growth plates
is avoided
• Circumferential irradiation of a limb is avoided
• Gonadal avoidance or additional shielding (for the testes)
• Irradiation of the Achilles tendon is usually avoided
• For pelvic tumors, distention of the bladder prior to each
day's treatment can reduce the amount of small bowel in the
radiated field

29. Proton beam therapy
• One way to reduce the volume of normal tissue
irradiated is with charged particle irradiation using
protons.
• Compared to photon beam irradiation, proton beam
therapy permits the delivery of high doses of RT to the
target volume while reducing the radiation dose received
by normal tissues distal to the target.

30. • Because of the proximity of the spinal cord, the dose to
vertebral body primaries using conventional photon
irradiation has been often limited to 45 Gy. Proton beam
therapy permits the delivery of higher doses while
respecting spinal cord constraints.
• When used for pelvic lesions, proton beam therapy is
associated with better sparing of the
intestine, rectum, bladder, pelvic bone marrow, and
femoral head as compared to photon irradiation Proton
beam irradiation.

31. RT schedule
Data from the University of Florida suggest that
hyperfractionated RT (1.2 Gy twice daily with a six hour
interfraction interval) may be associated with less long-term
toxicity .
Limited field sizes with hyperfractionated high-energy RT could
minimize long-term complications and provide superior
functional outcomes.

32. IORT — A benefit for intraoperative RT (IORT) has been
suggested in retrospective series involving a small number of
patients .
• However, peripheral nerves are dose-limiting tissue structures
for IORT, so the risk of severe neuropathy and soft tissue
necrosis must be considered if this approach is used.

33. SEQUELAE OF TREATMENT
• Acute effects — Acute reactions are those that occur during
or shortly after the completion of RT. The most prominent
affect tissues within the radiated field that contain rapidly
dividing cells, and include
• desquamation of the skin,
• myelosuppression,
• mucositis, diarrhea, nausea, and cystitis.
• Patients receiving whole lung irradiation are at risk for
radiation pneumonitis.
Acute reactions are usually self-limited and subside within
10 to 14 days of RT completion

34. Late effects :
• Younger, prepubertal children are at greatest risk for
radiation-induced arrest of bone growth. Sparing of
uninvolved epiphyseal plates minimizes limb shortening after
RT of extremity lesions.
• RT doses above 60 Gy are associated with markedly increased
rates of soft tissue induration and fibrosis
• High-dose circumferential irradiation of an extremity is
associated with edema, fibrosis, and compromised limb
function . This can be avoided by sparing of an adequate strip
of tissue.
• Weight-bearing bones are at risk for pathologic fractures. The
highest risk is within the first 18 months of RT completion

35. Second malignancy after RT
• OSTEOSARCOMA
With protocols utilizing lower doses of RT and tailored RT fields
suggest that the magnitude of the risk is somewhat lower.
• 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 )

36. SUMMARY of RT in EWINGS
Localized disease — For patients with localized EFT, local and systemic
therapy are both necessary to achieve cure.
• For patients who lack a function-preserving surgical option because
of tumor location or extent, and those who have clearly
unresectable primary tumors following induction
chemotherapy, recommend RT
• Bulky tumors in difficult sites (eg, the pelvis); in this setting, RT can
be given either preoperatively or postoperatively, based upon
institutional protocols
• If there is residual microscopic or gross disease after surgery, or
inadequate surgical margins.
• Adjuvant hemithorax irradiation is indicated in patients with highrisk chest wall primary tumors (close or involved margins, initial
pleural effusion, pleural infiltration, and intraoperative
contamination of the pleural space)

37. Advanced disease: For patients with metastatic EFT, RT rather
than surgery for treatment of the primary site in most
patients
• because of the potential for reduced pulmonary relapse and
improved event-free survival, and the low rate of pulmonary
toxicity, bilateral low-dose lung irradiation (15 to 18 Gy) is
recommended

38. NCCN GUIDELINES V1.2014

39. NCCN CONT..

40. Patients who lack a function-preserving surgical option because of tumor location or extent, and those who have clearly unresectable primary tumors following indu
NCCN CONT…….

41. SURVIVAL

44. Conclusion
• Second most common childhood bone tumor.
• Multimodal treatment approach
• Overall survival with localized disease (55%) and metastatic disease
22%
• Radiation responsive tumor
• LOCAL THERAPY includes SURGERY/RT. Surgery when feasible first
choice of local therapy
• There are no randomized trials that have directely compared
Radiotherapy to surgery for local control of Ewing’s sarcoma.
• Refinements in diagnostic imaging, RT planning, and newer techniques
(tailored field size, hyperfractionated treatment schedules, IMRT, proton
beam irradiation) have resulted in better limb function among long-term
survivors, and excellent functional results in the majority of patients
following RT for EFT.

45. THANK YOU…….