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.

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.

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.

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

Precision Technology in Radiotherapy Delivery

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

CHARGED PARTICLE BEAM THERAPY

ProtonNeutronHeliumCarbon ion

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

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.

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.

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

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.

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#.

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

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

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

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 %

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.

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.

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/#

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

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

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.

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…

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.

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

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

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

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.

POST OP RT PLANNING

SURGICAL BED +(RESIDUAL TUMOR)+ 2-

4 CM MARGINS.

DOSE : MICROSCOPIC DISEASE- 50.4 Gy MACROSCOPIC RESIDUAL – 55.8Gy

PALLIATIVE RT

PAIN PALLIATION – ADVANCED DISEASE.

ISOLATED BONE SECONDARIES.

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

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.

Disseminated Myeloma

Dose : 2250 cGy / 225-cGy fractions, 5 days per week 10#s.

In general, patients with rapidly advancing disease receive lower doses.

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.

Radionuclide therapy

Is presently used for disseminated bony metastases for long term pain relief.

Radionuclide in practice: 89 strontium 153 Samarium – EDTMP 32 phosphorus.

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%).

IMRT

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