RT in Bone Tumors
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ROLE OF RADIATION THERAPY IN ROLE OF RADIATION THERAPY IN THE MANAGEMENT OF BONE THE MANAGEMENT OF BONE
TUMORS.TUMORS.
PROF. R. MOHAN RAM MD., PROF. R. MOHAN RAM MD., DMRTDMRT
HEAD OF THE DEPARTMENT OF HEAD OF THE DEPARTMENT OF RADIATION ONCOLOGY,RADIATION ONCOLOGY,
BIR&O, MADRAS MEDICAL COLLEGE.BIR&O, MADRAS MEDICAL COLLEGE.
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INTRODUCTION
Radiation therapy is generally not considered
as a primary modality in the management of
the osteosarcoma, but there is ample historic
and growing modern evidence that these
tumors are responsive to radiation as well.
Surgical resection remains the main stay in the
management of primary bone tumors.
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Multi modality treatment approach
includes RT in,
Primary bone tumors of the axial skeleton and
facial bones - functional and cosmesis
preservation.
Ewing's sarcoma and peripheral primitive
neuroectodermal tumors of bone can be
treated by definitive radiation.
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Three-dimensional conformal radiation
techniques using multiple fields, multileaf
collimation, and intensity-modulated IMRT beams
are useful aids to optimize the homogeneity of
the dose within the target volume while sparing
adjacent normal structures allowing treatment of
previously inaccessible areas.
Techniques of radiation delivery
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Precision Technology in Radiotherapy Delivery
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BRACHYTHERAPY
Technologic enhancements now also permit full
three-dimensional planning for brachytherapy with
dose-volume histograms and other tools. Real
application of brachytherapy to the treatment of
primary bone tumors is awaited, although some
very preliminary experience in recurrent disease is
available using high dose-rate perioperative
approaches
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CHARGED PARTICLE BEAM THERAPY
ProtonNeutronHeliumCarbon ion
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In proton beam irradiation,
high-doses of radiation can be made to conform precisely to
the target by the high-energy release at the end of proton
beam's range.
This provides improved dose distribution in deep locations
compared to photon irradiation.
It is available only at a handful of sites, although an
increasing number of treatment units will be available in the
future.
CHARGED PARTICLE BEAM THERAPY
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Neutron radiotherapy has been
emphasized by certain groups because of
overcoming hypoxic radioresistance: lower oxygen enhancement ratio compared to x-
rays and the consequent attractive possibility of
overcoming the biologic phenomenon of limited
curability of malignancy due to hypoxia with x-
rays.
Lack of cell cycle / phase sensitivity.
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OSTEOSARCOMA
Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy is the current standard of care for osteogenic sarcoma.
Irradiation has not been considered part of the primary management of OS for nearly 20 years.
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RT is used in,
Patients with tumor in inaccessible sites.
• Pelvis
• Axial skeleton.
• Facial bones
Elderly patients refusing surgery.
Patients who require palliation.
Dose : 66-70 Gy in 1.8-2Gy/#.
EBRT using high energy Mega voltage photon beams.
IMRT – in axial tumors.
Brachytherapy – in mandible OS.
CURRENT ROLE OF RT IN MANAGEMENT OF OSTEOSARCOMA
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Post op RT –
Not indicated when surgery is complete with negative margins
in accessible sites.
Indicated, where negative margin could not be possible.1
Dose : 50 – 60 Gy/1.8-2Gy/#.
ref: DeLaney et al –
MGH data
Pre op RT – no role.
Extracorporeal irradiation.
Palliative RT.
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FACIAL BONES
OS of the facial bones appear to have a
different biology compared to those located
elsewhere –lower tendency to metastasize
and hence have better prognosis.
Dose : 350cGy/10#.
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EXPERIMENTAL IN-SITU RADIOTHERAPY IN EXTREMITY
SARCOMAS IN PATIENTS WHO REFUSED AMPUTATION AFTER
NEO-ADJUVANT CHEMOTHERAPY.
Radical fractionated RT - 60 Gy was given
For patients who responded well to chemotherapy by imaging
and fall in Alk. Phos levels.
They responded to RT as well. Achieved a 5 year survival of 90
%.
Study by Blokhin cancer research centre, Moscow
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For metastatic bony sarcomas
Unresectable tumors at axial sites.
Advanced inoperable lesions of extremities.
Dose :
EBRT
30Gy/300cGy/#/10#s/2weeks.
20Gy/400cGy/#/5#s.
Bone seeking targeted radionuclide therapy.
PALLIATIVE RT
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89 Strontium:
Administered as strontium chloride, usually 4 mCi
intravenously.
Strontium is incorporated in to the inorganic matrix
of bone with increased uptake in metastatic tumor.
Response within 2 weeks and is sustained for up to 6
months. One third of patients remained totally pain
free.
Re-treatment is safe. The main disadvantage is the
cost which is very high. Toxicity is less.
RADIONUCLIDE THERAPY
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32 Phosphorus: 7 to 40 mCi in fractionated doses usually.
The main advantage is cost – less compared with other isotopes and readily available.
The disadvantage is the reported incidences of pan cytopenia, induction of Leukemia as the bone marrow dose is high the range of skeletal absorbed dose is 25-63 rad / mCi.
Response rate is 70-80%.
153 samarium – EDTMP: Response occurs within 2 weeks of administration, sustained
between 4 – 40 weeks.
Response rate is 60 – 80 %
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DOSE AND VOLUME CONSIDERATIONS FOR DEFINITIVE RT (surgically inaccessible sites)
Treatment volume : shrinking fields :
Initial field : initial tumor volume (MRI) + generous margin (2-3cm)
for microscopic extent + 2 cm in total for patient movement.
(45-50 Gy)
Boost field : residual tumor volume at the time of RT + 2 cm
( up to 70 Gy ).
Extremity fields should be planned with a strip of un-irradiated
tissue out of the beam to allow for lymphatic and venous return
and to decrease morbidity.
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EXTRACORPOREAL BONE IRRADIATION.
Extracorporeal bone irradiation has been used with success where custom prosthesis or allograft could not be used.
Hong et al, Australia reported 16 patients with primary bone tumors between 1996-2000.
All patients had en-bloc resection of the affected bone after neoadjuvant chemotherapy.
50Gy single dose was delivered to the resected specimen and reimplanted using appropriate internal fixation.
No local recurrence or graft failure at 19 months follow-up. One patient had amputation due to chronic osteomylitis. Among the 10 patients, functional outcome at 18 mo follow-
up was good to excellent.
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CHONDROSARCOMA Dedifferentiated chondrosarcoma is treated as osteosarcoma Mesenchymal chondrosarcoma is treated as Ewing's sarcoma For low grade histology's treatment is with surgery/RT. Indications for RT:
Inaccessible tumor Where clear margins are not achievable. Recurrence
Dose : 50-70 Gy/ 200cGY/#/5days/week.
5 year survival – RT alone – low grade 48% high grade 22%.
PRINCESS MARGARET EXPERIENCE :
85 % local recurrence after surgery alone.
LC – 50 % after curative RT.
25 % were disease free at 15 years.
50 – 55 Gy in 180-200 cGy/#
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Massachusetts General Hospital published results
of 519 patients treated with proton therapy.
5 yr Local Control
73 % for chordoma
98 % for chondrosarcoma
Dose – 66-83 CGE (cobalt gray equivalent)
Proton beam therapy- chordoma and chondrosarcoma
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Because complete surgery is rarely possible, Post op RT , dose of 50 – 70 Gy is indicated.
Surgery + RT - DFS -- 6.6 years
Surgery alone - DFS -- 4.1 years
Proton therapy gives promising results.
CHORDOMA
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GIANT CELL TUMOR OF BONE The standard treatment
Curettage, cryosurgery
Radiotherapy can be given in unresectable sites.
GCT is not radio resistant.
At Princess Margaret Hospital,
local control was achieved in 13 of 14 patients with GCT treated
with one course of megavoltage radiation.
The disease in 12 patients was controlled for longer than 5
years
There was no malignant transformation.
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Dose :
EBRT : 35-55 Gy in conventional daily fractions.
Local control rates:
range from 75% to 85% in more recent series.
Giant Cell Tumor Of Bone contd…
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Rare Tumors MFH of bone
treatment similar to osteosarcoma.
Fibrosarcoma
primary arm - surgery.
RT in inoperable or post op residue.
Dose : 66-70Gy.
Malignant hemangio endothelioma
surgery + RT 50 – 60 Gy.
Lymphoma
40 Gy to the entire bone + 5 Gy boost to the original tumor +
systemic chemo.
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EWING’S SARCOMA
INDICATIONS FOR RT: After induction chemotherapy
DEFINITIVE RADIATION THERAPY
Tumors where Resection is Impossible or where only an intra-lesional resection is achievable Patient with poor Surgical risk Patient refusing surgery
SURGERY IS THE PREFERRED ARM where wide or marginal resection is possible
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INDICATIONS FOR RT: After induction chemotherapy
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
For intra-Lesional Resection
For marginal Resection
For wide-resection with Poor Histological response to Neo-adjuvant Chemotherapy
– (>10% viable tumor cells in the specimen)
Based on CESS-81, CESS-86, EICESS-92 Studies : Schuck et al,IJROBP-1998 & 2003Based on CESS-81, CESS-86, EICESS-92 Studies : Schuck et al,IJROBP-1998 & 2003
INDICATIONS FOR RT: After induction chemotherapy
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PLANNING
DEFINITIVE RT Phase 1:
Gross tumor in bone and soft tissue (pre chemo MRI definition) + 2-4 cm longitudinal margins + 2 cm lateral margins.
Dose:45 Gy/180cGy/#
Boost phase : Reduced 1-2 cm margins
Up to total dose of 55.8Gy.
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POST OP RT PLANNING
SURGICAL BED +(RESIDUAL TUMOR)+ 2-
4 CM MARGINS.
DOSE : MICROSCOPIC DISEASE- 50.4 Gy MACROSCOPIC RESIDUAL – 55.8Gy
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PALLIATIVE RT
PAIN PALLIATION – ADVANCED DISEASE.
ISOLATED BONE SECONDARIES.
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MULTIPLE MYELOMA
Indications for RT
Plasmacytomas :
As primary treatment in localized presentations (solitary
plasmacytomas of bone and extramedullary plasmacytomas)
Multiple Myeloma:
For palliation of pain from bone lesions of multiple Myeloma,
RT is the best arm, though Chemotherapy takes care of
systemic disease.
For prevention of pathologic fractures in weight-bearing bones
For relief of spinal cord compression or nerve root compression
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Solitary Plasmacytomas Of Bone And
Extramedullary Plasmacytomas
Dose 50 Gy/200cGy/#
Field to sufficiently cover the primary
tumor, all its extensions, and the regional
lymph nodes with a 2- to 3-cm margin.
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Disseminated Myeloma
Dose : 2250 cGy / 225-cGy fractions, 5 days per week 10#s.
In general, patients with rapidly advancing disease receive lower doses.
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SECONDARY BONE METASTASIS
Goal: The goal is to prevent or relieve symptoms especially
pain and compression and to improve quality of remaining life.
Dose schedules used in bone mets: Localized irradiation:
30Gy / 10 #.20Gy / 4-5#.800 cGy / single fraction.
Hemi body irradiation:Previously hemi body irradiation is used for disseminated bony
lesions. It has been given up because of associated complications and improper maintenance of aseptic measures.
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Radionuclide therapy
Is presently used for disseminated bony metastases for long term pain relief.
Radionuclide in practice: 89 strontium 153 Samarium – EDTMP 32 phosphorus.
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Pain Response rates (EBRT)
41% of patients – attains at least 50% pain relief at one month.
The goal of freedom from symptoms until death is reported for few long-term survivors (about 10%).
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IMRT
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