RADIATION ONCOLOGY

1. INDICATION,EVIDENCES AND RT
TECHNIQUES IN OSTEOSARCOMA
DR.SHUCHITA
DNB RESIDENT

3. Classification
PRIMARY or SECONDARY
 PRIMARY OSTEOSARCOMAS are
 Conventional /classic osteosarcoma (high
grade, intra medullar y)
 Low-grade intramedullary osteosarcoma
 Parosteal osteosarcoma
 Periosteal osteosarcoma
 High-grade surface osteosarcoma
 Telangiectatic osteosarcoma, and
 Small cell osteosarcoma.
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4. Classification
 SECONDARY OSTEOSARCOMAS
 Osteosarcomas occurring at the site of another disease
process.
 more common in >50 years of age
The most common causes are
Paget disease
Previous radiation treatment
Other associated conditions are
Fibrous dysplasia
Bone infarcts
Osteochondromas
Chronic osteomyelitis
Dedifferentiated chondrosarcomas
Osteogenesis imperfecta
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5. INTRODUCTION
• Osteosarcoma is most common primary bone cancer (35%).
• Osteosarcoma has a bimodal distribution with cases arising
during the teenage years as well as cases associated with
other conditions (Paget Disease, fibrous dysplasia) that
arise in an older (age >65 yrs) population.
• Osteosarcoma is more common in boys (> girls) and in
blacks (> whites).
• Highly malignant tumor of mesenchymal origin.
• Incidence – 1 to 3 per million per year

6. INTRODUCTION
• Osteosarcoma arises most frequently in the
appendicular skeleton (80% of cases) at the metaphyseal
portions of the distal femur, tibia, and humerus.
• Osteosarcoma spreads hematogenously, with the lung
being most common metastatic site.
• Osteosarcoma is associated with Li-Fraumeni syndrome
(germline inactivation of p53) as well as retinoblastoma.

7. DISTRIBUTION OF PRIMARY &
SECONDARIES

8. Classic High Grade Osteosarcoma
 These aggressive, high-grade tumors begin in an
intramedullary location, but may break through the
cortex and form a soft-tissue mass.
 The histologic hallmark - malignant osteoblastic spindle
cells producing osteoid, presence of woven bone with
malignant appearing stromal cells
 subtypes -
o osteoblastic,
o chondroblastic
o fibroblastic 8

9. Clinical Presentation
• Pain – Progresssive pain
due to microinfarction
night pain in 25 %
• Swelling - Palpable mass is noted in up to 1/3
of patients at the first visit
• Fever, malaise or other constitutional symptoms
are not typical of osteosarcoma
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10. Plain X-ray
 Lesions are usually permeative
 Associated with destruction of the cancellous and
cortical elements of the bone
 Ossification within the soft tissue component, if
tumour has broken through cortex
 Borders are ill defined
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INVESTIGATIONS:-

11. Plain X-ray
 Periosteal reaction may appear as the characteristic
Codman triangle.
 Extension of the tumor through the periosteum may
result in a so-called “sunburst” appearance.
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12. Other investigations
 MRI
 CT
 Angiogram
 Bone scan
 Laboratory studies
 Biopsy
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13. MRI
• Best modality for documenting
the extent of a primary bone
and soft tissue mass is an MR
scan
• Should include the entire
involved bone so as to make
sure that skip metastases are
not present
• Specialized cross-sectional
studies, including MR
neurograms, MR angiograms,
and CT angiograms are
important to assist with surgical
planning.
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14. CT-scan
• A dedicated chest CT scan
is perhaps the most
sensitive way to exclude
distant disease in the
lungs (Lung mets at
presentation 10%)
• CT scanning also has
proven utility in studying
axial primary sites, as well
as in predicting
pathologic fracture risk
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15. Angiogram
• Determine
vascularity of the
tumour
• Detect vascular
displacement
• Relationship of
vessels to the tumour
• Not of much use after
CT or MR
angiography, only
used when
embolization is
required
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16. Bone scan
• Bone mets <5%
• Helps to determine
polyostotic (multifocal)
involvement and
metastatic disease
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17. PET
• PET or PET/CT scan quantifies metabolic
activity in the primary site and helps to
exclude occult metastases.
• The utility of [F-18]-FDG PET/CT scanning in
the management of patients with bone
sarcoma is well established

18. Laboratory studies
• Full blood count, ESR, CRP.
• LDH (elevated level is associated with poor
prognosis)
• ALP (highly osteogenic)
• Platelet count
• Electrolyte levels
• Liver function tests
• Renal function tests
• Urinalysis
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19. Biopsy
• Supreme caution must be taken to avoid contamination
• Guided FNA or core procedures- These method has the
advantage maximizing sampling throughout the mass while
minimizing contamination
• Whenever an open biopsy procedure is chosen, careful
attention must be paid to incisional length (short) and
placement (in line with the definitive resection procedure)

23. Treatment
 Current standard of care
Radiological staging
Biopsy to confirm diagnosis
Preoperative chemotherapy
Repeat radiological staging (access chemo response, finalize surgical
treatment plan)
Surgical resection with wide margin
Reconstruction using one of many
techniques
Post op chemo based on preop response
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24. TREATMENT OF OSTEOSARCOMA
• SURGERY
• The main goal of surgery is to safely and completely
remove the tumor.
• Historically – amputation.
• Over the past few years - limb-sparing procedures
have become the standard, mainly due to advances
in chemotherapy and sophisticated imaging
techniques
• Limb salvage procedures now can provide rates of
local control and long-term survival equal to
amputation.
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25. SURGERY
• Pelvic tumors require a hemipelvectomy for en bloc
resection.
• Adjuvant radiation has been used to improve outcomes
in patients with incomplete resections of pelvic tumors.
• Spinal tumors are difficult to resect with negative
margins. Typically, an en bloc resection with
vertebrectomy is performed, combined with mechanical
stabilization.
• Postoperative radiation therapy used when negative
margins cannot be obtained, particularly when there is
microscopic dural involvement.

26. Amputation
• Amputation involves
removal of the limb
with a safe margin
• It should not be viewed
as a failure of
treatment, but rather as
the first step towards
patient’s return to a
more comfortable and
productive life
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27. Amputation
Indication
1. Grossly displaced pathologic fracture
2. Encasement of neurovascular bundle
3. Tumor that enlarges during preop chemo and
is adjacent to neurovascular bundle
4. Palliative measure in metastatic disease
5. If the tumor has caused massive necrosis,
fungation, infection, or vascular compromise.
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28. Limb salvage surgery
• Removing the tumor with a normal cuff of tissue
surrounding it while preserving vascular and nerve
supply to the extremity.
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29. Limb salvage surgery
• Surgical guidelines-
– No major neurovascular involvement
– En block removal of all previous biopsy site and
potentially contaminated tissues with wide
margins
– Resection of bone 3 to 4 cm beyond abnormal
uptake, as determined by CT, MR and bone scan
– Adequate motor reconstration

30. Limb salvage surgery
• Skeletal defect must be
reconstructed by
•Endoprosthesis (most
common) – replacing the
removed bone with a metal
implant
•Allograft (cadaveric) bone
Vascularized bone acquired
from the patient
•Allograft-prosthetic
composite constructions
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31. Rotationplasty
• Compromise between amputation and limb salvage
• most commonly used for osteosarcomas of the distal
femur in skeletally immature patients
• It is a procedure where the neurovascular structures
and distal aspect of the limb (leg) are retained, and
re-attached to the proximal portion after the tumor
has been removed.
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32. Rotationplasty
• For functional purposes, the distal segment is turned 180
degrees so that the ankle joint functions as a knee joint, thus
converting an above-knee to a below-knee amputation in
order for prosthetic use to be maximized
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33. CHEMOTHERAPY
• Before routine use of CT, 5 year survival was <20%
• 50% patient developed metastasis (lung) within 6 month
• Advantages of neoadjuvant chemotherapy -
• Regression of the primary tumor, making a limb
salvage operation easier.
• May decrease the spread of tumor cells at the time
of surgery
• Effectively treating micrometastases at the earliest
time possible.

34. • It avoid tumor progression, which may
occur during any delay before surgery.
• Given for about 3-4 weeks before
definitive procedure
• Chemotherapy plays an important role for all
patients with intermediate- and high-grade
tumors.

35. Chemotherapy
• The drugs used most often to treat osteosarcoma
– HD-Methotrexate
– Doxorubicin (Adriamycin)
– Cisplatin or carboplatin
– Ifosfamide
– Bleomycin
– Cyclophosphamide
– Actinomycin-D
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36. CHEMOTHERAPY
• Eilber et al.:-
1. 59 patients with nonmetastatic osteosarcoma
randomized to surgery followed by
observation versus adjuvant chemotherapy.
2. DFS at 2 years was 55% with chemotherapy
and 20% with observation (p < .01).
3. OS was also superior at 2 years: 80% versus
48% with and without chemotherapy,
respectively (p < .01).

37. CHEMOTHERAPY
• Link et al.:-
1. 36 patients with nonmetastatic, high-grade
osteosarcoma randomized to observation
versus adjuvant chemotherapy after primary
surgery.
2. DFS at 2 years was 66% with chemotherapy
and 17% with observation (p < .001).

38. CHEMOTHERAPY
• POG 8651 randomized patients with nonmetastatic,
high-grade osteosarcoma to neoadjuvant
chemotherapy followed by surgery or surgery followed
by the same chemotherapy.
• 5-year relapse-free survival was not statistically
different between the two groups (65% vs. 61%,
respectively), nor was the rate of limb salvage (55% vs.
50%, respectively).
• This trial did not show improved outcomes with
neoadjuvant chemotherapy, it did show equivalence
and established a benchmark for comparison with
future trials.

39. EURAMOS I (AOST 0331):- This ongoing trial is
evaluating the benefit of additional chemotherapy
after preoperative and postoperative chemotherapy
consisting of methotrexate, doxorubicin, and cisplatin.
Patients with a poor response to preoperative
chemotherapy are randomized to the addition of
ifosfamide and etoposide, whereas those with a good
response to preoperative chemotherapy are
randomized to the addition of interferon.
•In the past 20 years, standard treatment has evolved
to the routine use of NACT and adjuvant CT.

40. RADIATION THERAPY
• Highly radioresistent tumor
• Radiation therapy has very limited role in
Ostesarcoma
INDICATION
• Unresectable primary tumors
• Incompletely resected tumors with positive
margins
• Patients who refuse surgery
• For palliation of symptomatic metastases

41. Radiation Therapy Techniques
• SIMULATION AND FIELD DESIGN:-
• 3-D treatment planning with the aid of presurgical
and postsurgical imaging is used to define gross
tumor volumes and areas of subclinical disease.
• Typically, a 2-cm margin is used for axial tumors,
which can be extended to 4 to 5 cm for extremity
tumors.
• Spare 1.5-2cm strip of skin in extremity,to prevent
edema

42. Radiation Therapy Techniques
• Try to exclude the skin over anterior tibia, due to
poor vascularity.
• The radiation technique used, either 3D-CRT or
IMRT, should be tailored to the individual
patient.
• Dose to uninvolved organs should be minimized
to prevent late organ dysfunction, as should the
integral dose to minimize risk of secondary
malignancy.

43. • Intraoperative radiation therapy has been used to
deliver dose directly to close or involved surgical
margins
• Proton particle therapy has been used in an
attempt to escalate radiation dose, particularly in
unresectable tumors
• Radionuclide therapy-
– Rhenium
– Strontium
– samarium
• Used for palliation of extensive bone metastases
with good effects

44. DOSE
• 60 Gy in 2-Gy fractions used for
microscopically involved margins
• 66 Gy is used for macroscopic residual
disease and
• 70 Gy is used for inoperable tumors.
• Radiation can be given concurrently but is
usually delivered after chemotherapy due to
increased acute toxicity with concurrent
administration.

45. Cooperative Osteosarcoma Study Group
(COSS)
• Total of 175 pts with histologically proven osteosarcoma
irradiated over the period of 1980−2007. 100 pts were eligible
for analysis.
• Indication for RT was :- a primary tumor in 66, a local
recurrence in 11, and metastases in 23 pts. 94 pts got external
photon therapy; 2 pts, proton therapy; 2 pts, neutron therapy;
and 2 pts, intraoperative RT.
• The median dose for external RT was 55.8 Gy (30–120). All the
pts received chemotherapy in accordance with different COSS-
protocols.
• The median follow-up :- 1.5 (0.2–23) years.

46. Cooperative Osteosarcoma Study Group
(COSS)
• Survival and local control rates at 5 years were calculated.
• The overall survival rate after biopsy was 41% at 5 years,
while the overall survival rates after RT for the whole group,
for treatment of primary tumors, local recurrence, and
metastases were 36%, 55%, 15%,0% respectively.
• Local control for the whole group was 30%. Local control
rates for combined surgery and RT were significantly better
than those for RT alone (48% vs. 22%, p = 0.002).
• Local control for treatment of primary tumors, local
recurrence, and metastases were 40%, 17%, and 0%
respectively.

47. Schwarz et al.
• Reported on an analysis of 100 patients treated
with radiation therapy in the COSS registry.
• Local control and overall survival for the whole
group were 30% and 36%, respectively, at 5 years.
• Local control was significantly better when
surgery was combined with radiation compared
to radiation alone: 48% vs. 22%, respectively (p =
.002)

48. Machak et al.
• Reported on a series of 187 patients with nonmetastatic
osteosarcoma treated with induction chemotherapy.
• 31 patients with non-metastatic osteosarcoma who refused
surgery and were treated with induction chemotherapy f/b
radiation to a mean dose of 60 Gy.
• OS,PFS,MFS(Metastasis free survival) at 5 yr were mean of
61%,56%,62% respectively.
• Patient who were responder had OS and MFS at 5 yrs of
90% and 91% respectively v/s non-responders 35% and
42% respectively(p=0.005, and p=0.005respectively)
• However, local progression-free survival was 31% at 3 years
and 0% at 5 years for nonresponders.

49. De Laney et al.
• Reported on 41 pts with osteosarcoma who were
either not resected or were excised with close or
positive margins and who underwent RT with
external beam photons (median dose of 66 Gy)
• No definitive dose response, although dose>55Gy
had higher local control(p=0.11)
• RT is more effective for patients with microscopic
and minimal residual disease

50. COMPLICATIONS
• Permanent weakening of affected bone
• Scoliosis
• Decreased range of movement due to fibrosis or joint
involvement
• Vascular changes resulting in greater sensitivity to
infection
• Lymphedema
• Osteoradionecrosis

51. EXTRACORPOREAL IRRADIATION (ECI)
• It consists of en-bloc removal of the tumor bearing bone segment,
removal of the tumor from the bone ,irradiation, and
re-implantation back in the body.
• First reported by Spira et al in 1968
• ECI has several potential advantages.:-
1. The affected bone segment is removed from the body and
irradiated and therefore, avoidance of radiation injury to the
un-irradiated bone, muscles, joint, and other healthy tissues of
the body.
2. The delivery of very high doses of radiation to tumor bearing
bone by ECI, which is otherwise not possible in the intact bone.
These higher doses in the range of 50-300 Gy, are lethal to the
remaining tumor cells and therefore, reduce the risk of
recurrence.
3. It provides an anatomically size-matched graft for biological
reconstruction.

52. Extra corporeal Irradiation
• Several case series from India (DN
Sharma,AIIMS) and outside world showed
excellent long term local control in
Osteosarcoma, Ewings sarcoma and
chondrosarcoma
• 50 Gy in single fraction is used

53. Davidson et al (2005)
• Reported a series of 50 patients with different
malignant bone tumor mainly ESFT (21
patients) and OS (16 patients) using en bloc
resection and ECI (50 Gy).
• The mean time of ECI process was 35 min.
With a mean follow-up of 38 months (range
12-92), 84% patients were alive without any
disease and only 8% developed LR.

54. Poffyn et al (2011)
• Recently published a retrospective analysis
of 107 patients with 108 malignant or locally
aggressive bone tumors treated by ECI with
300 Gy, and re-implantation of the bone as
an orthotopic autograft.
• At 5 year follow-up, there was no LR and
64% of patients had well healed graft. The
0% LR rate could be due to relatively very
high dose of ECI (300 Gy) used in their study.

56. Conclusion
• Radioresistant
• Surgery is main stay of treatment
• NACT improved the respectability without
compromising the Survival
• Radiation has role in margin positive,
unresectable and palliative settings

57. THANK YOU