osteosarcoma is radio-resistant tumor.but chemoradiation is effective tool to

1. OSTEOSARCOMA
Dr. AADITYA PRAKASH
DNB Resident, Radiation Oncology
BMCHRC, Jaipur

2. INTRODUCTION
• Osteosarcoma is most common primary bone cancer (35%).
• Osteosarcoma is most common radiation induced sarcoma.
• Osteosarcoma has a bimodal distribution as a function of age, 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).

3. INTRODUCTION
• Osteosarcoma arises most frequently in the appendicular skeleton (80% of
cases) at the metaphyseal portions of the distal femur, tibia, and humerus.
• Osteosarcoma broadly classified in 3 histologic subtypes:-intramedullary,
surface and extra-skeletal.
• High grade intramedullary osteosarcoma (conventional /classic) refers to
the most common (80% of all cases) variant of osteosarcoma, which
typically presents within areas of rapidly proliferating skeletal bone.
• Osteosarcoma is associated with Li-Fraumeni syndrome (germline
inactivation of p53) as well as retinoblastoma.

4. INTRODUCTION
• Other types of less common osteosarcomas include telangiectatic,
small cell, juxtacortical, periosteal, and high-grade surface sarcomas.
• Juxtacortical osteosarcoma refers to a set of more rare osteosarcoma
variants that arise adjacent to the outer surface of cortical bone.
• Osteosarcoma spreads hematogenously, with the lung being most
common metastatic site.

5. CLINICAL PRESENTATION
• Pts with osteosarcoma typically
present with localized bone pain
(often associated with an injury) of
several months duration and a soft
tissue mass/swelling.
• Osteosarcoma is derived from
bone-forming mesenchyme, and is
described as a malignant
sarcomatous stroma associated
with the production of osteoid
bone.

6. DISTRIBUTION OF PRIMARY & SECONDARIES

7. PROGNOSTIC FACTORS (NCCN)
• TUMOR SITE AND SIZE
• PATIENT AGE
• PRESENCE & LOCATION METASTASES
• HISTOLOGICAL RESPONSE TO CHEMOTHERAPY
• GENDER
• TYPE OF SURGERY & SURGICAL MARGINS
• BMI ( COG )
COSS
EOI RCT

8. WORKUP/STAGING
• HISTORY AND PHYSICAL
EXAMINATION
• MRI +/- CT OF PRIMARY SITE
• CHEST CT SCAN
• PET SCAN AND /OR BONE SCAN
• MRI or CT OF SKELETAL
METASTATIC SITES
• LDH
• ALP

9. • The elevated periosteal reaction
cause Codman’s triangle to
form.
• In osteosarcoma, periosteal
new bone formation, with the
blastic component shows bony
sunburst pattern.

11. Musculoskeletal Tumor Society (MSTS) staging
system

12. TREATMENT OF OSTEOSARCOMA
SURGERY
• Complete en bloc resection of tumor is the mainstay of local
treatment of osteosarcoma.
• Surgical resection is performed either by amputation or a limb-
sparing approach and has a 5% local failure rate.
• For extremity lesions, limb preservation is preferred and can be
accomplished in the majority of cases.

13. 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.

14. CHEMOTHERAPY
• Chemotherapy plays an important role for all patients with
intermediate- and high-grade tumors.
• 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).

15. 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).

16. 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.

17. Memorial Sloan-Kettering Cancer Center T10 regimen is frequently
used for nonprotocol patients :- high-dose methotrexate, doxorubicin,
bleomycin, cyclophosphamide, and actinomycin D.
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.

18. RADIATION THERAPY
INDICATION
• Unresectable primary tumors
• Incompletely resected tumors with positive margins
• Patients who refuse surgery
• For palliation of symptomatic metastases

19. Radiation Therapy Techniques
• 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.
• These margins can be restricted at natural tissue and fascial boundaries.
• 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.

20. 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.
• Chemotherapy should not be interrupted to deliver local
radiation therapy.
• Radiation can be given concurrently but is usually delivered
after chemotherapy due to increased acute toxicity with
concurrent administration.

21. 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.
• The median age was 18 (3–66) years.
• 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.
• In addition, a group of 17 pts received bone-targeted radionuclide therapy by
samarium-153-EDTMP-therapy alone or in combination with external 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.

22. 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%, and 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.
• Local control for pts given an addition of samarium-153-EDTMP was poor,
though not statistically significant . A dose of over 60 Gy had no significant
effect on local control.

23. 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)

24. Machak et al.
• Reported on a series of 187 patients with nonmetastatic
osteosarcoma treated with induction chemotherapy.
• 31 patients refused surgery and were treated with radiation to a
mean dose of 60 Gy.
• Local control was related to response to induction chemotherapy.
There were no local recurrences in 11 patients who had a good
response to chemotherapy.
• However, local progression-free survival was 31% at 3 years and 0% at
5 years for nonresponders.

25. 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 (10–80 Gy))
and/or protons at the Massachusetts General Hospital (MGH).
• Local control rates, according to the extent of resection, were 78.4%
for gross total resection, 77.8% for subtotal resection, and 40% for
biopsy only.

26. OTHER MODALITIES
• Intraoperative radiation therapy has been used to deliver dose
directly to close or involved surgical margins.
• Radionuclide therapy with rhenium, strontium and samarium has
been used for palliation of extensive bone metastases with good
effects.
• Radium-223 dichloride is bone seeking radiopharmaceutical ,under
investigation for treatment of metastatic or recurrent osteosarcoma.
This agent is approved in US for treating bone mets assoc. with
castration resistant prostate cancer.

27. 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, there are limited reports available in the literature.
• 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.
4. It is cost effective as compared to the prosthetic devices.
5. It has psychological advantage as patients feel that their own bone is being used as
prosthesis.

28. 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. The mean MSTS score was 77.

29. 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.

30. • radiological images and operative
photographs of a 10 year old boy diagnosed
with osteosarcoma of lower end of right
femur that underwent extracorporeal
irradiation (ECI).
• (a) (plain radiograph) and
• (b) (reconstructed computed tomography
scan) showing the tumor at the lower end of
femur.
• (c) the resected bone segment from which
the tumor has been removed. The same was
packaged and sent for ECI.
• (d) the operated limb after the resection of
the bone segment

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