Departmental Seminar on Management of Bone tumours

1. BONE TUMOURS
Dr. Abhilash Gavarraju
JR-II

2. NORMAL BONE
m
Anatomic regions of long bones relate to the growth plate and include the
epiphysis, which is the region between the growth plate and the nearest joint;
the diaphysis, which is the shaft region of the bone between the two growth
plates; and the
metaphysis, which is the region of bone adjacent to the growth plate on the
diaphysial side.

3. INTRODUCTION
• Malignant tumours that arise from the skeletal
system are rare, representing 0.001% of all new
cancers.
• In 2010, an estimated 2650 new cases and 1460
related deaths were expected.
• Osteosarcoma, Chondrosarcoma and Ewing’s
Sarcoma are the most common comprising 35%,
30% and 16% of cases respectively.

4. CLASSIFICATION
Histological type Malignant tumors
Hematopoietic Myeloma, Reticulum cell sarcoma
Chondrogenic Primary, Secondary, Dedifferentiated,
Mesenchymal
Osteogenic Osteosarcoma, Parosteal OS
Idiopathic Ewing’s, Malignant GCT,
Adamantinoma, Fibrous Histiocytoma
Fibrogenic Fibrosarcoma
Notochordal Chordoma
Vascular Hemangioendothelioma,
Hemangiopericytoma

6. ENNEKING STAGING SYSTEM
• IA (G1, T1, M0) : Low grade intracompartmental
• IB (G1, T2, M0) : Low grade extracompartmental
• IIA (G2, T1,M0) : High Grade intracompartmental
• IIB (G2, T2, M0) : High Grade extracompartmental
• IIIA (G1/2, T1, M1) : Intracompartmental, any grade
with metastasis
• IIIB (G1/2, T2, M1) : Extracompartmental, any grade
with metastasis

7. TNM AND AJCC STAGING
• Primary Tumor (T)
Tx – Primary cannot be assessed
T0 – No evidence of primary
T1 – Tumor </= 8 cm
T2 – Tumor > 8 cm
T3 – Discontinuous tumor in primary bone site
• Regional Lymph Nodes (N)
Nx – Regional LN’s cannot be assessed
N0 – No regional LN metastasis
N1 – Regional LN metastasis

8. • Distant Metastasis (M)
Mx – Distant mets cannot be assessed
M0 – No distant mets
M1a – Lung only
M1b – Other distant sites
• Histological Grade (G)
Gx – Grade cannot be assessed
G1 – Well differentiated – low grade
G2 – Moderately differentiated – low grade
G3 – Poorly differentiated
G4 - Undifferentiated

9. Stage T N M Grade
IA T1 N0 M0 G1,2 low
grade, Gx
IB T2 N0 M0 G1,2 low
grade, Gx
T3 N0 M0 G1,2 low
grade, Gx
IIA T1 N0 M0 G3,4 high
grade
IIB T2 N0 M0 G3,4 high
grade
III T3 N0 M0 G3
IVA Any T N0 M1a Any G
IVB Any T N1 Any M Any G
Any T Any N M1b Any G

10. OSTEOSARCOMA

11. • It is the MC malignant bone tumour.
• Histological hallmark – Production of malignant
osteoid.
• “Osteosarcoma, which is a true cancerous
degenration of bone, manifests itself in the form
of a white or reddish mass, lardaceous and firm
at an early stage of the disease; but presenting at
a later period, points of softening, cerebriform
matter, extravasating blood, and white or straw
coloured fluid of a viscid consistence in its
interior”
Introduction

12. • Most commonly causes patients to die from
pulmonary metastatic disease.
• Most arise as solitary lesions within the fastest
growing areas of the long bones of children.
• Top 3 affected areas – Distal Femur, Proximal
Tibia, Proximal Humerus.
• Synchronous Osteosarcoma – Multiple sites may
become apparent within a period of 6 months.
• Metachronous Osteosarcoma – Multiple sites may
be noted over a period longer than 6 months.
• Multifocal OS when occurs tends to be in patients
younger than 10 yrs.

13. Epidemiology
• Incidence slighly higher in blacks and males.
• Incidence increases steadily with age, increasing
more dramatically in adolescence,
corresponding with the growth spurt

14. Etiology
• Exact cause in unknown
• Rapid bone growth is a predisposing factor
• Typical location in the metaphyseal area
adjacent to the growth plate of long bones.
• Radiation exposure is the only known
environmental risk factor.
• Genetic predisposition

15. Pathophysiology
• Can occur in any bone, usually in the extremities
of long bones near metaphyseal growth plates
• Other significant locations are Skull and Jaw
and Pelvis
• Variants – Conventional types(Osteoblastic,
Chondroblastic, Fibroblastic), Telangiectatic,
Multifocal, Parosteal and Periosteal

16. Clinical Features and Physical
Examination
• MC symptom – Pain, particularly pain with
activity
• Often, there is a history of trauma
• Telangiectatic type – MC associated with
pathological fractures
• Pain may result in a limp
• Lung mets and respiratory symptoms indicate
extensive involvement
• Palpable mass may or may not be present
• Decreased range of motion

17. Workup
• Labs
- LDH, ALP (Prognostic Significance)
- CBC, Platelets
- LFT, KFT, Electrolytes
- Urinalysis
Most lab studies relate to the use of chemotherapy
- Elevated ALP at diagnosis are more likely to
have pulmonary metastasis
- In patients without mets, those with an elevated
LDH are less likely to do well than are those with
a normal LDH

18. • Imaging Studies
1. Plain films – CODMAN’S TRIANGLE
SUNBURST APPEARANCE
2. CT – Primary Lesion and Chest ; Delineate the
location and extent of the tumor and is critical
for surgical planning
3. MRI – Assess extent of disease and soft tissue
masses and skip lesions; Single most
important study for accurate surgical staging
4. Tc99 Bone Scan
5. ECHO/MUGA Scan

21. Diagnostic Procedures
• Biopsy and Wide Resection are the two main
procedures performed
• Incisional biopsies or core needle biopsies are
the MC types of biopsies performed
• Wide resection is the goal for patients in whom
primary tumor resection is contemplated`

22. Osteosarcoma
Management

23. • A complete radical, surgical, en bloc resection of
the cancer, is the treatment of choice in
osteosarcoma
• About 90% of patients are able to have limb
salvage surgery, complications particularly
infection, prosthetic loosening and non-union or
local tumor recurrence may cause the need for
further surgery or amputation
• Standard therapy is a combination of limb
salvage orthopedic surgery and a combination of
chemotherapy

24. Surgery
Classification of Surgical Procedures for Bone Tumors
Margin Local-limb sparing Amputation
Intralesional Curettage or
debulking
Debulking amputation
Marginal Marginal excision Marginal amputation
Wide Wide local excision Wide through bone,
amputation
Radical Radical local resection Radical disarticulation

25. Limb Sparing Surgery
Prerequisites & method
• No major neurovascular tumor involvement
• Wide resection of the affected bone, with a
normal muscle cuff in all directions
• En bloc removal of all previous biopsy sites
and potentially contaminated tissue
• Resection of bone 3 to 4 cm beyond abnormal
uptake, as determined by CT or MRI and bone
scan
• Resection of the adjacent joint and capsule –
expandable endoprosthesis
• Adequate motor reconstruction, accomplished
by regional muscle transfers

26. Limb-sparing Surgery - Steps
Operation
1. Resection of tumor
2. Skeletal reconstruction
3. Soft tissue and muscle transfers:
▫ Cover and close the resection site & to restore
motor power
▫ Distal tissue transfers are not used because of the
possibility of contamination

27. Limb Sparing Surgery
Contraindications
• Major Neurovascular involvement
• Pathologic fractures
▫ Spread of tumor cells via the hematoma beyond accurately determined limits- risk of
local recurrence increases
▫ If a pathologic fracture heals after neoadjuvant chemotherapy, a limb-salvage
procedure can be performed successfully
• Inappropriate biopsy sites
▫ Contamination of normal tissue planes and compartments
• Infection
• Skeletal immaturity
▫ The predicted leg-length discrepancy should not be greater than 6 to 8 cm
▫ Upper extremity reconstruction is independent of skeletal maturity
• Extensive muscle involvement

28. Chemotherapy for Bone Sarcomas
• Before routine use of systemic chemotherapy for the
therapy of osteosarcoma, fewer than 20% of patients
survived more than 5 years - recurrent disease
developed in 50% of patients, almost exclusively in the
lungs, within 6 months of surgical resection
• Findings of randomized clinical studies completed in the
1980s comparing surgery alone to surgery followed by
chemotherapy demonstrated conclusively that the
addition of systemic chemotherapy improved survival in
patients presenting with localized high-grade
osteosarcoma
• Four most important drugs used for the treatment of
osteosarcoma include high-dose methotrexate (HD-
MTX), adriamycin (ADM), cisplatin (CDDP), and
ifosfamide (IFOS)

29. Considerations for Presurgical and Postsurgical Chemotherapy
Timing of
Chemother
apy
Advantages Disadvantages
Pre
op
Early institution of systemic therapy against
micrometastases
High tumor burden
Reduced chance of spontaneous emergence of drug-
resistant clones in micrometastases
Increased probability in the selection of
drug-resistant cells in primary tumor, which
may metastasize
Reduction in tumor size, increasing the chance of limb
salvageProvides time for fabrication of customized
endoprosthesis
Delay in definitive control of bulk
disease; increased chance for
systemic dissemination
Less chance of viable tumor being spread at the
time of surgery
Psychological trauma of retaining
tumor
Individual response to chemotherapy allows
selection of different risk groups
Risk of local tumor progression with
loss of a limb-sparing option
Post
op
Radical removal of bulk tumor decreases tumor
burden and increases growth rate of residual
disease, making S phase–specific agents more
active
Delay of systemic therapy for
micrometastases
Decreased probability of selecting a drug-
resistant clone in the primary tumor
No preoperative in vivo assay of
cytotoxic response
Possible spread of viable tumor by
surgical manipulation

30. Which Is Optimal?
Pediatric Oncology Group Study POG-8651
• 45 patients of osteosarcoma were
randomly assigned to presurgical
chemotherapy, and 55 patients were
randomly assigned to immediate surgery
• No difference observed among the two
arms of the study
• Rates of limb salvage and survival same in
both arms
Goorin AM, Schwartzentruber DJ, Devidas M 2003

31. Why Favor Pre-operative
Chemotherapy?
• Important survival implications of
histological response to such therapy
• Good responders have better prognosis
• Greater than 90% necrosis and less than
90% necrosis in tumor histology after
chemotherapy differentiate good and
poor responders after 10 to 12 weeks of
preoperative chemotherapy
• Easy surgical resectability

32. Evidence of Response to
Chemotherapy
• Clinical: pain, alkaline phosphatase (AP) levels
decrease. The tumor shrinks, especially if
significant matrix is not present
• Radiology:increased ossification of tumor osteoid,
marked thickening and new bone formation of
the periosteum and tumor border
• Angiography: vascularity decreases markedly

33. Summary of Chemotherapy
• In nonmetastatic high-grade osteosarcoma -adjuvant
chemotherapy with HD-MTX and at least two other drugs
among the four most-active drugs in osteosarcoma can be
expected to lead to a 75% 5-year survival among good
histologic responders (greater than 90% necrosis) and 55%
among poor histologic responders (less than 90% necrosis)
• Timing of chemotherapy does not improve survival, though
it does help in prognostic stratification of patients

34. Chemotherapy Regimes
• First Line Therapy (Primary/NACT/Adjuvant)
1. Cisplatin-Doxorubicin
Cis – 100mg/m2 i.v D1
Dox – 25mg/m2 i.v D1-3
(3 cycles NACT  surgery on D63  3 cycles
Adjuvant)
2. Cisplatin-Ifosfamide-Epirubicin
Cis – 100mg/m2 i.v D1
Epi – 90mg/m2 i.v D1
Ifos – 2g/m2 i.v over 2 hrs D2-4
(3 cycles NACT and 3 cycles Adjuvant)

35. 3. Doxorubicin-Dacarbazine
Dox – 15mg/m2 D1-4
Dacarex – 250mg/m2 D1-4
4. MAID
Dox – 15mg/m2 D1-4
Ifos – 2g/m2 D1-3
Dacarex – 250mg/m2 D1-4
Mesna – 2.5 mg/m2 D1-4
5. Etoposide-Ifosfamide

36. • Methotrexate
- High dose Mtx 8-12g/m2 along with leucovorin
- Pretreatment creatinine should be atleast
70ml/min
- Alkalization of urine before High Dose Mtx
- Mtx is dissolved in 5%D with final conc of about
1g/100ml.
- Leucovorin rescue 24 hrs after the start of Mtx
15-25mg P.O every 6 hrs for atleast 10 doses

37. • Second Line Therapy
1. Docetaxel-Gemcitabine
Doce – 75-100mg/m2 i.v D8
Gem – 675mg/m2 D1,8
2. Cyclophosphamide-Etoposide
Cyclo – 500mg/m2 D1-5
Etop – 100mg/m2 D1-5
3. Cyclophosphamide-Topotecan
Cyclo – 250mg/m2/dose
Topo – 0.75mg/m2/dose
Each given as 30 min infusion daily x 5 days

38. • High dose Samarium-153 ethylene diamine
tetramethylene phosphonate
(153Sm-EDTMP) for relapsed or refractory
disease beyond 2nd line therapy
1,3,4.5,6,12,19 or 30 mCi/kg

39. ROLE OF RADIOTHERAPY
• RT does not play a major role
• Typically a 2 cm margin is used for axial tumors which
can be extended to 4-5 cm for extremity tumors
• 60Gy in 2Gy fractions is typically used for
microscopically involved margins
• Macroscopic residual disease – 66Gy
• Inoperable tumors – 70Gy
• RT can be given concurrently but is usually delivered
after chemotherapy
• IORT and Proton therapy have also been used
• RT is extremely beneficial in patients requiring
palliation of metastatic bony sarcomas; tumors at axial
sites, which are unresectable and advanced inoperable
lesions of the pelvis or extremitites.

40. Radiotherapy
• Traditionally considered radio resistant
• Generally not used in the primary
treatment
• Used for patients who have refused
definitive surgery, require palliation, or
have lesions in axial locations
• Tumors of axial skeleton and facial
bones are treated by a combination of
limited surgery and radiotherapy,
because the goals of treatment are
functional and cosmesis preservation
• In the post operative setting when
residual disease is present (margin
+ve, LVI)

41. Palliative Setting
• Metastatic and recurrent osteosarcomas have
poor prognosis
• Various combinations of the 4 drugs have been
tried but 5-year survival rates have been in the
range of 20%

42. Radiotherapy- Guidelines
• Appropriate imaging studies to define tumor location
correlated with surgical pathologic findings
• Physical fluoroscopic simulation or computed tomography–
based virtual simulation
• Patient immobilization and/or stereotactic localization
• Megavoltage conventional external-beam delivery
• High radiation dose with appropriate fractionation
• Large radiation field/volumes with "shrinking field" techniques
to reduce volumes beyond threshold doses for microscopic
disease
• Beam-shaping devices (mounted shielding or multileaf
collimation)
• Beam modifiers for contour shape—compensating filters,
wedges, or dynamic wedge or beam segmentation with or
without intensity modulation
• Multiple fields to be treated per day

43. Dose and Volume
Considerations
• Entire clinical and radiographic extent of tumor plus a generous
margin for microscopic or subclinical extension of disease
• Irradiated field should encompass at least the volume of tissue that
would be resected, plus an allowance of approximately 2 cm in total
for patient movement
• Extremity fields should be planned with a strip of tissue deliberately
out of the beam to allow for lymphatic and venous return and to
decrease morbidity
• Shrinking field volume technique is recommended

44. Shrinking Field Technique
Entire bone treated up to 40 Gy in
2 Gy Fractions at 5 fractions per
week
Field reduction to cover
tumor volume with margin
up to 66-70 Gy

45. Newer Techniques Of Radiotherapy
3-D Conformal Radiotherapy
IMRT
Particle beam radiotherapy

46. CHONDROSARCOMA

47. Introduction
• Mesenchymal origin
• Predominantly made of cartilage
• 2nd MC primary malignant tumour of bone
• Different types – Conventional (90%)
Dedifferentiated
Clear Cell
Mesenchymal
Juxtacortical
Secondary

48. Pathophysiology and Genetics
• Primary – Arise de novo
• Secondary – Arise from preexisting cartilage
Occur in Ollier disease, Mafucci Syndrome,
Multiple hereditary exostosis, Paget’s disease,
Radiation Injury
• High proliferation rate on Ki-67 IHC
• Loss of heterozygosity at many loci

49. Histological Grading
• Grade I (Low Grade)
• Grade II (Intermediate)
• Grade III (High)
• 10-15% of Grade II lesions metastasize
• >50% of Grade III lesions metastasize
• Dedifferentiated chondrosarcomas are more
aggressive than Grade III chondrosarcomas

50. Epidemiology
• Conventional chondrsarcomas account for nearly 80-
90% of all chondrosarcomas and 20-27% of all primary
bone sarcomas
• Predilection for axial skeleton
• Pelvis and ribs – 45%
Ilium – 20%
Femur – 15%
Humerus – 10%
• Dedifferentiated chondrosarcomas (10%) – Femur is
the MC site involved
• Clear cell variant - <5%; predilection for ends of long
tubular bones involving epiphysis; proximal femur f/b
proximal humerus

51. Clinical Presentation
• Deep, dull achy pain
• Nocturnal Pain
• Joint restriction if tumor is close to the joint
• >50% of patients with dedifferentiated
chondrosarcomas present with pathological
fractures
• Mean interval from pain to diagnosis is 19.4
months for Grade I and Grade II and 15.5
months for Grade III lesions

52. Plain Radiographs
• Typical appearance – Discrete calcification
• Usually large >5cm
• Endosteal scalloping
• Cortical thickening
• Perpendicular periosteal new bone formation
that has a sunburst appearance
• Stippled or punctate calcification

53. MRI, CT, Bone Scan and USG
• It is the INVESTIGATION of choice
• Helps delineate extent of soft tissue involvement
• MRI also helpful for confirming or diagnosing
recurrence at a surgically treated site
• CT may be useful for subtle calcifications and
improves visualization of bony destruction

54. Biopsy
• Directed at areas that may harbour foci of high
grade tumor
• FNAC
• Core Biopsy – Tru-Cut biopsy or Core Needle
biopsy
• Risk of seeding of the biopsy tract is high so
procedure should be done meticulously

55. Treatment
• RT and CT play limited roles
• Diffuse mets is an indication for systemic RT or
CT
• May be useful in dedifferentiated
chondrosarcoma
• Surgery with clear margins remains the primary
treatment
• Complete wide surgical excision is the preferred
method

56. Role of RT
• No Level 1 evidence exists for RT in
chondrosarcoma
• RT indicated to improve on high local rates after
incomplete resection of high risk tumors
• Doses of 50Gy preop and 60-66Gy postop for
close or positive margins are typically used
• >70Gy dose is needed for definitive treatment

57. NCCN Recommendations
• Base of Skull Tumors
- Postop therapy or RT for unresectable disease -
>70Gy
• Extracranial sites
- Preop RT (19.8-50.4Gy) may be considered if
positive margins are likely f/b Postop RT with
70Gy in R1 resection and 72-78Gy in R2
resection
- Postop RT 60-70Gy in high grade lesions with
positive margins
- High dose therapy with specialized techniques
recommended

58. Outcome and Prognosis
• Grade I – 90% survival at 5 yrs
• Grade II – 81% survival at 5 yrs
• Grade III – 29% survival at 5 yrs
• Overall 5 yr survival rate for conventional
chondrosarcomas is 48-60%
• Dedifferentiated chondrosarcoma is highly
lethal, 10% survival rate after one year

59. EWING’S SARCOMA

60. Introduction
• 2nd MC primary tumor of bone in childhood
• ESFT include Ewing’s Sarcoma, Peripheral
PNET, Neuroepithelioma, Atypical Ewing’s and
Askin Tumor
• Ewing Sarcoma tumors include Ewing sarcoma,
Askin tumor and peripheral PNET
• MC combination – EWS exon 7 fused to FLI1
exon 6 occurs in 50-64% of tumors

61. Etiology
• Thought to arise from cells of the neural crest,
possibly mesenchymal stem cells
• Exact origin in unknown
• MC translocation – t(11;22)
• It has been found that relatives of patients with
Ewing’s sarcoma have an increased incidence of
neuroectodermal and stomach malignancies

62. Epidemiology
• Incidence higher in whites by 9 times
• Incidence peaks in late teenage years
• Overall 27% cases occur in first decade, 64% in
2nd decade and 9% in 3rd decade

63. Signs and symptoms
• Localized pain
• Back Pain (indicates paraspinal or
retroperitoneal tumor)
• Palpable mass
• Fever and Weight Loss (Systemic sympts)

64. Histology and IHC
• Ewing sarcoma are small, round, blue cell
tumors. They can be nor differentiated, as
reflected in rosette formation
• IHC markers include MIC2 (12E7) antigen
(CD99), which is characteristic but NOT
pathognomonic
• Muscle, lymphoid, and adrenergic markers
should be negative.

66. Diagnosis
• CBC, Blood Cultures, CRP, ESR, LDH
• Cytogenetic and molecular studies
• Histology
• Plain Radiography
• CT
• MRI
• Bilateral Bone Marrow Biopsy
• Chest CT Metastatic
• Whole Body MRI Work up
• FDG-PET (in suspected cases)

67. Treatment
• Lasts 6-9 months and consists of alternating
courses of 2 regimes
• VAC/IE
V – 2mg/m2 i.v
A – 75mg/m2 iv bolus infusion daily
C f/b Mesna – 1200mg/m2 daily
I – 1800mg/m2 daily for 5 days with Mesna
E – 100mg/m2 daily for 5 days with Mesna
• Patients often develop episodes of fever and
neutropenia

68. Chemotherapy Regimes
• VAI
Vinc – 1.5mg/m2 i.v D1,8,15,22
Adria – 30mg/m2 i.v D1,2,43,44
Ifos – 3000mg/m2 i.v D1,2,22,23,43,44
Actinomycin D – 0.5mg/m2/d x 3 i.v D22,23,24
• VIDE
Vinc – 1.5 mg/m2 i.v D1
Ifos – 3000 mg/m2 i.v D1,2,3
Dox – 20mg/m2 i.v D1,2,3
Etop – 150mg/m2/d x 3 i.v D1,2,3
Followed by Mesna Prophylaxis and G-CSF support

69. • Currently, an open study within the Children’s
Oncology Group (AEWS1031) is evaluating the
efficacy of adding vincristine, topotecan, and
cyclophosphamide to the interval compressed 5-
drug backbone for patient with nonmetastatic
Ewing sarcoma (NCT01231906)

70. Advantages of Induction Chemotherapy
• Evaluation of the effectiveness of the regime
• Shrinkage of the soft tissue mass
• Surgeons can achieve better margins
• Bone healing which takes place during
chemotherapy diminished the risk of
pathological fracture if RT is used later
• Response rates are as high ass 90%

71. Role of Surgery
• For definitive therapy, limb salvage surgery is
preferable over amputation, but amputation may
be an option for younger patients with lesions of
the fibula, tibia and foot
• In older patients, lesions of the proximal fibula,
ribs, scapula, clavicle and wing of the iliem are
easier to resect
• Lesions of the bones of the hands and feet may be
resectable with a ray resection

72. • No randomized study has been performed
to define whether local control is better
accomplished with surgical resection or
radiotherapy

73. Radiation Therapy
• Fields encompassing the primary tumor with a 3-
to 5-cm margin
• >60 Gy if primary radiotherapy is being used
• 55.8 Gy for gross and 45 Gy for microscopic
residual disease after primary treatment

74. Results of Therapy
• Addition of CT to local therapy increased survival
from <10% to >40% at 5 yrs for patients with
localized disease at diagnosis
• SEER data confirms gradual improvement in
survival over time
• IESS-I reported addition of Doxorubicin improved
local control
• The first CCG/POG intergroup study showed an
improvement in survival in the intensified arm for
patients with localized disease and large primary or
pelvic tumors
• Early RT is preferable to late RT post chemotherapy

75. High Dose Therapy with Stem Cell rescue
• Invetigational megatherapy and stem cell rescue
using high-dose CT with and without total-body
irradiation
• Increasingly accepted for patients with metastatic
disease or recurrence in Europe
• Different regimes – melphalan, etoposide, busulfan,
carboplatin and thiopeta
• Compartmental irradiation to doses upto 54Gy and
high dose CT and stem cell rescue reported a 5 yr
survival rate of 54%

76. Radiation Induced Sarcoma
• Secondary sarcomas arising in irradiated normal
bone: from 5% to 10% at 20 years from
diagnosis
• Doses greater than 60 Gy :excess risk of
secondary bone sarcomas
• Risk of developing a secondary bone tumor in the
irradiated field was negligible at doses below 48
Gy
• The treatment of radiation-associated sarcoma is
wide resection, when possible, combined with
adjuvant chemotherapy

77. MALIGNANT GIANT CELL TUMOR

78. Introduction
• Rare benign primary tumor of the bone accounting
for about 3-5% of all primary bone tumors
• Strong tendency for local recurrence and that may
metastasize to the lungs
• Usually occurs between 20-40 yrs of age
• Distal Femur and Proximal Tibia are the most
common primary sites
• Malignant transformation to high grade
osteosarcoma observed in rare cases

79. Workup
• History and PE
• CT is useful to define the extent of cortical
destruction
• MRI is the preferred modality to assess
extension of tumors into adjacent tissue and
neurovascular structures
• Chest CT to identify metastatic disease
• Bone Scan
• Biopsy to confirm diagnosis

80. Treatment
• Surgery
- Wide excision and intralesional curettage for
resectable tumors
- Wide excision associated with a lower risk of
local recurrence than curettage
- Wide excision associated with poor functional
outcome and greater surgical complications
- Stage I and II – Curettage is TOC
- Sage III and IV – Wide Excision preferred

81. • Radiation Therapy
- Used as primary treatment or in combination
with surgery to improve local control and DFS
for patients with marginally resected,
unresectable, progressive or recurrent disease
- 50 to 60Gy for metastatic disease
- Increased risk of malignant transformation
following RT has been noted in some studies

82. • Systemic Therapy
- DENOSUMAB – significant activity in
unresectable or recurrent GCTB
- FDA approved in June 2013 for treatment in
adults and skeletally mature adolescents with
GCTB that is unresectable or where surgical
resection is likely to result in severe morbidity
- Recent Phase II trial data suggested FDG-PET to
be a sensitive tool for early detection of tumor
response to Denosumab treatment

83. NCCN Recommendations
• Localized Disease
- Intralesional excision with or without an
affective adjuvant
- Serial arterial embolizations in extremity lesions
- Few case reports reported efficacy of INF and
Peg-INF
- RT to be used in patients not amenable to above
procedures
- Stable/Improved disease – Intralesional
Excision is recommended

84. • Metastatic Disease
- Intralesional excision is recommended for
resectable metastatic disease
- Denosumab, INF, RT, Observation are included
as options

85. CHORDOMA

86. Introduction
• Rare tumors that arise from embryonic
notochordal elements along the length of the
neuraxis at developmentally active sites
• <1% of CNS tumors
• Thought to arise from ectopic notochordal
elements
• Slow growing but locally aggressive tumors
leading to tissue destruction and death
• Mets are recognized but are uncommon

87. Epidemiology
• 0.2% of all CNS tumors
• 2-4% of all primary bone neoplasms
• Sacrum (50%) > Clivus > Spine Axis
• M:F = 2:1
• Intracranial chordomas present in a much
younger age group than their spinal
counterparts

88. Clinical Presentaiton
• Sacrum – LBA, Lower extremity pain
- Autonomic symptoms in 50% pts particularly
rectal dysfunction and urinary incontinence
- Palpable sacral mass
• Intracranial – Diplopia, Headache, CN Palsies
C.N VI and sensory V are MC
• Lower vertebra – Pain, Bladder dysfunction, Lower
extremity weakness
• Cervical vertebra – Hoarseness, Dysphagia
• Time span from symptoms to diagnosis averages 10
months

89. Pathology
• Conventional (Majority)
• Chondroid chordoma (5-15%) – Better prognosis
• Dedifferentiated chordoma (<5%) – More
aggressive, faster growing and more likely to
metastasize

90. Treatment
• Surgery has been the primary approach
• Complete en bloc resection with negative
margins achieves local control in 70-80% cases
• If margins are positive, failure rate >70%

91. Radiotherapy
• Considered relatively radioresistant
• >66Gy dose required
• Difficult to achieve with conventional EBRT techniques
• IMRT, SRS associated with good local control rates in cranial
and extracranial chordmas
• Best results have been achieved with a combination of Surgery
and High dose Proton Therapy exploiting the concept of Bragg
peak
• Brachytherapy can be used for recurrent tumors of the base of
skull or adjacent to the spine when a more aggressive surgical
exposure is offered

92. NCCN Recommendations
• Base of Skull
- Postop RT or RT for unresectable disease 70Gy
or higher
- Consider Postop RT for R0 resections
• Mobile Spine
- Consider preop RT (19.8 to 50.4 Gy) and postop
RT to total dose of 70Gy (depending upon
normal tissue tolerance)

93. Systemic Therapy
• Not sensitive to chemotherapy except for the
potentially dedifferentiated portion of high
grade dedifferentiated chordomas
• Phase II trial of 56 pts treated with IMATINIB,
70% has stable disease
• ERLOTINIB and LAPATINIB effective in
IMATINIB resistance

94. • Patients with recurrence can be managed with
surgery and/or RT and/or Systemic Therapy.
• The guidelines have included Imatinib with or
without cisplatin or sirolimus, erlotinib,
sunitinib and lapatinib (for EGFR +)

95. BONE METASTASES

96. Introduction
• Common occurrence in the event of
malignancy
• Third most common site of distant
metastases after liver and lung
• Cause significant and debilitating pain
• Pathological fracture and spinal cord
compression
• Significant morbidity
• Multimodality approach
• Aims at alleviation of pain and prevention of
future complications
• Palliative irradiation should be delivered
such that side effects should not be more
distressing than the symptoms to be treated

97. Primary site Prevalence%
Breast 45-85
Prostate 54-85
Lung, 32-40
Thyroid 28-60
Kidney 33-40
GI 5-13

98. • Sites of preference of bone mets
- Spine (69%)
- Ribs
- Pelvis (41%)
- Skull (14%)
- Long bones ends (25%)
• Spinal Location
Thoracic 60 to 70%
Lumbar 15 to 30%
Cervical 10 to 15%
Multiple 20 to 35%

99. • Types of Bone mets
• Osteolytic lesions :
• Multiple myeloma
• Mets from – Breast
- Kidney
- Thyroid gland
• Osteoblastic lesions :
• Prostate
• Breast
• Hodgkins disease
• Mixed lesions :
• Breast

100. Clinical Features
• Pain MC
▫ initially well-localized/ diffuse ache/ radiculopathy/ difficult
movement
• Biologic Pain
▫ Tumor's presence in the bone.
▫ The release of inflammatory mediators.
▫ Irritation of nerve endings.
• Functional Pain
▫ Caused by the mechanical weakness of the bone.
▫ loss of structural integrity in blastic lesions
• The development of functional pain is a marker
for a bone at risk for fracture.

101. Diagnostic Evaluation
• Careful History
• Physical examination including complete
Neurological examination
• Routine hematological investigations including
▫ Alkaline phosphatase
▫ Tumor markers
 PSA in prostate ca
 CA15.3 breast ca
▫ Serum Ca++
• Biopsy must be performed to verify the
diagnosis before initiation of treatment.
 Bx/ FNAC/ open Bx
 CT guided/ non weight bearing region

102. Imaging
• Plain radiography (XR)
• Bone scan
• Computed tomography (CT)
• Magnetic resonance imaging (MRI)
• PET-CT

103. Plain Radiographs
• Most specific but least sensitive.
• Inexpensive and easily obtained
• Basis for the initial evaluation,
planning, and follow-up
• Evaluate the structural integrity of
bone and the risk of impending
pathologic fracture
• Important in decision making, plain
radiography should be the first test
ordered to evaluate bone pain.
• Loss of trabeculations and cortical
erosion is characteristic

104. Bone Scan
• Highlights regions of bone turnover with areas
of new bone deposition.
• 72% to 84% sensitive in detecting occult bone
lesions
• Integral in the evaluation of a patient with bone
pain.
• Detects functional changes
• Not specific/ no structural detail
• Radiographs required
• Lytic lesions appear cold

105. CT Scan
• Not a primary tool/ a useful adjunctive study
• 3 D evaluation of bone integrity for planning in
shoulder and pelvic lesions
• Extent of cortical destruction
• Soft tissue component
• Identify a target for needle biopsy
• Bony anatomy well in the spine
• No epidural extension and neural compression
• No extent of medullary involvement

106. MRI
• Marrow involvement
• Early detection
• Neural compression
• Differentiates pathologic compression #
from osteoporotic compression #s of
the spine.
• Difficulty differentiating infection,
inflammation, and metastatic disease of
bone.
• MRI is not a stand-alone study and
images require correlation with plain
radiographs.

107. PET-CT
• Unknown primary
• Multiple sites of metastatic disease.
• Although the PET imaging modality shows
promise, it is currently only an investigational
tool for most cancers.
• Correlation with structural imaging is required
for treatment planning.

108. Planning
• Explain patient about the procedure
• Positioning
• Immobilization
• Simulation
• Dose prescription
• Treatment
• Patient care during RT.

109. Immobilization
• No formal immobilization used
• Cervical spine – head fixation
• Adequate analgesia before & after RT
Position :
• Most Comfortable to Pt
• Cervical vertebral mets : Supine
• Thoracic vertebral mets : Prone
• Lumbar vertebral mets : Prone
• If pt is not able to lie prone, can be simulated in
supine position & treated from under couch

110. Radiation Portals
• Cervical spine :
Lateral portals – reduce morbidity by sparing upper
aerodigestive structures
• Thoracic spine :
Direct Posterior portal
• Lumbar spine :
Direct Posterior portal
AP / PA portal if pt thin
• Ribs :
Electron beams
Tangential photon beams

111. Margins
• Superior margin : one vertebra
above the highest involved
vertebra (2-3cm)
• Inferior margin : one vertebra
below the lowest involved
vertebra (2-3cm)
• Width : to include transverse
process on both sides
( appr. 7-8 cm)
• For long bones : Margins 2 -
3cm above and below

112. Depth of Prescription
• To be decided with available images
• Direct posterior portal – distance from skin to
Ant. Vertebral body of the involved vertebra
• AP/PA Portal – mid separation
• Bilateral portal - mid separation
• Cervical spine – 3cm
• Thoracic spine – 4cm
• Lumbar spine – 5-6 cm

113. Dose Prescription
• 8Gy/1#, 20Gy/5#, 30Gy/10#, 37.5Gy/15# &
40Gy/20#
(depending upon expected survival of the pt)
( Dirk Rades et al JCO, 2005 )

114. General Instructions
• When bone mets from extremities to be treated,
important to spare a strip of soft tissue along the
entire length of extremity to allow lymphatic return
from distal portion of limb
• While irradiating pelvic bones -
- Maximal sparing of small bowel, bladder &
rectum
- Also closely monitor blood counts
• Careful documentation with simulator films, skin
tattoos, photographs, portal diagrams

115. WIDE FIELD RT/HEMIBODY IRRADIATION
• HBI – a form of Subtotal Body Irradiation
• One half of body irradiated
• Intent of Treatment – Palliative
• Indication : disseminated bony metastasis
involving either half of body
• Most common primaries associated : Breast,
Lung, Prostate

116. Types of HBI
• UHBI (above umbilicus) –
Skull, Cervical, Dorsal,
Lumbar spine upto L3,
Ribs, Sternum, Clavicle,
Scapula, Upper limbs
• LHBI (below umbilicus) –
Lumbar spine below L3,
Sacrum, Pelvis, Lower limbs
• MHBI (diaphragm to obturator
foramen)
Lumbosacral spine, Pelvis, Femoral
heads

117. Treatment Parameters
• Borders
- UHBI :
Upper – Air (3 cm above head)
Lower – L3 / L4(Upper border of
umbilicus)
- LHBI :
Upper – L3 / L4
Lower – 3-4 cm below patella
- MBI :
Upper - D6 (domes of diaphragm) /
D10 (insertion of diaphragm)
Lower – Cover Obturator foramen
Go lower down if overt
disease present
Laterally, cover whole extent of body

118. • Portals – Parallel opposed AP/PA
• Energy – 6 MV photons
• Field Size – 40 cm x 40 cm
• Dose –
* UHBI – 6 Gy / 1 # Prescribed at average
* LHBI – 8 Gy / 1 # mid thickness depth on
* MBI – 8 Gy / 1 # central axis

119. SIDE EFFECT UHBI / MBI LHBI
Nausea / Vomiting (onset in hrs,
may last for days)
>80% without
antiemetics
<15%
Diarrhea (onset in hrs,
lasts for days)
less more
Hematological
(nadir :10-14 days, lasts 4-6
wks)
likely Slightly more
than UHBI
Pneumonitis
(16 wks)
At >7.5 Gy / 1 #

120. RADIOISOTOPES
• Bone seeking isotopes P32, Sr89, Sm153, Rh186,
Y90
• FDA approved Sr89-EDTMP, Sm153 EDTMP
• Radioactive tin and phosphorus : phase I/II
trials
• Sr-89: metastatic hormone-refractory prostate
and breast cancer

121. Advantages
▫ ease of administration,
▫ Treatment of multiple sites
▫ improved therapeutic ratio due to localization
to bone
▫ potential to combine with CT / EBRT
• No apparent substantial difference in palliative
efficacy of diff. radionucl.
• Only one reported randomized phase II trial
compared Sr and Re

122. Bisphosphonates
• First-generation compounds
▫ clodronate and etidronate
• Second-generation
▫ tiludronate and pamidronate
• Third-generation
▫ risedronate and zoledronate
• Pamidronate has been shown in several studies to
be effective in treating osteolytic disease, and
zoledronate has proven efficacy in treating
osteoblastic and osteolytic metastatic bone disease.

123. PRIMARY BONE LYMPHOMA

124. Introduction
• Most primary lymphomas are of NHL type and
of DLBCL subtype
• <1-2% of adult NHL and <7-10% primary bone
tumors
• Majority of cases are limited disease and occur
in adults 45-60 yrs of age
• Slight male predominance
• EBV, HIV and HHV-6 known to be associated
• Optimal treatment is unknown
• R-CHOP is commonly used regimen

125. Clinical Features
• Pain without antecedent trauma unrelieved by
rest
• Monostotis or Polystotic disease most often in
the long bones of adults
• Femur – MC location
• Vertebral column and pelvis other locations
• B symptoms – Fever, Night Sweats, Weight Loss

126. Diagnostic Evaluation
• Anaemia
• Elevated LDH
• Elevated ALP
• Elevated ESR
• Elevated Platelets
• Elevated Calcium Level

127. • In a review of Primary NHL of bone, 103 of 131
reported cases were DLBCL
• Other subtypes reported to a much lesser extent
• In children, DLBCL is the MC subtype, followed
by Lymphoblastic Lymphoma
• No specific immunophenotype has been
reported for Primary NHL of bone

128. Genetics
• Lima and colleagues reviewed 63 cases of
Primary DLBCL of bone by multiple modalities
and found rearrangements of BCL-2 and c-MYC
in a portion of their cases
• Of note, one of their cases showed a dual
rearrangement of c-MYC and BCL-2, a
molecular finding more classically seen in nodal
DLBCL

129. FIBROSARCOMA

130. • <5% of all primary bone tumors
• Mesenchymal origin
• Predominance of fibroblasts without tumor
osteoid or cartilage production
• Predilection for long bones
• High metastatic potential
• Treatment – Complete Surgical resection and
often with NACT/Adjuvant CT
• RT can be used for incompletely resected or
unresectable tumors

131. MALIGNANT FIBROUS HISTIOCYTOMA

132. • <5% of bone tumors
• Characterized by a mixture of spindle-shaped
fibroblastic cells in a storiform pattern and
admixed with mononuclear cells with histiocytic
morphology and anaplastic giant cells without
tumor osteoid or cartilage production
• Complete Surgical resection is the mainstay of
treatment
• Like Osteosarcoma, it has a high rate of
metastases
• Known to benefit from Chemotherapy