Recent advances in the management of osteosarcoma include improved imaging techniques like MRI and PET/CT that can better assess tumor extent and predict response to chemotherapy. Biopsies can now be performed using less invasive core needle techniques. Advances in local therapy include limb-sparing surgeries using smaller resection margins and joint-sparing techniques along with proton beam and heavy ion radiotherapy for inoperable tumors. Multi-agent chemotherapy continues to be the standard of care, with additions like ifosfamide and mifamurtide. Follow-up now relies more on chest X-rays compared to CT scans. Future areas of research focus on optimizing chemotherapy regimens and targeting pathways like PI3K/

1. Recent advances in
management of osteosarcoma
Dr.Bipul Borthakur,
Professor,
Dept. of Orthopaedics, SMCH

2. Overview
• Current concept
• Brief on tumour Definition
• Recent advances
1. Advances in imaging
2. Advances in biopsy techniques
3. Advances in local therapy of operable osteosarcoma
4. Advances in local treatment of inoperable osteosarcomas

3. 5.Advances in systemic treatment
6.Advances in surgery
7.Advances in treating osteosarcoma variants
8.Advances in follow-up
9.Future outlook.

4. Current concept
• Current standard treatment -Surgery + chemotherapy =
disease-free survival in approximately 60% of patients with
localized extremity disease and 20–30% for patients with
primary metastases or axial primaries.
Most patients are treated using a neoadjuvant approach, and
histologic response to preoperative chemotherapy has emerged
as an independent prognostic indicator.
While combined preoperative and postoperative chemotherapy
has never been shown to provide survival benefits over adjuvant
chemotherapy alone.

5. • Histologic response to chemotherapy in the surgical specimen
graded by Huvo’s system:
1. Grade I: 0–50% necrosis
2. Grade II: 51–90% necrosis
3. Grade III: 91–99% necrosis
4. Grade IV: 100% necrosis

6. Regimen used currently …
• Multiagent chemotherapy is the standard of care in
osteosarcoma.
Doxorubicin,
Cisplatin
high-dose methotrexate, have demonstrated antitumor activity
in osteosarcoma.

7. Current protocol for
Chemotherapy:
Neoadjuvant phase (for 3–4 cycles), followed by surgery and
subsequent postoperative or adjuvant chemotherapy.
Advantages of Preoperative chemotherapy
1.Immediately treat micro-metastatic disease
2.It provides a safety margin for resection and may permit
potentially less resection of normal tissue if there is a significant
response
3.It allows time for surgical plannin

8. Current Rx

9. Radiotheraphy
No longer plays a part of the standard treatment for primary
tumors.
Osteosarcoma being radio-resistant .Useful in a selected group
of patients.
Postoperative radiotherapy may be indicated in patients:
• With positive or close surgical margins especially for the sites
like pelvis, thorax, head and neck, etc.
.

10. Palliative radiotherapy
• Palliative radiotherapy may be useful in incurable or
metastatic patients for alleviation of local symptoms like pain,
bleeding, fungation or metastatic symptoms like dyspnea,
spinal cord compression, brain metastases,etc.

11. Surgical principle :
“Ensuring adequate local control is mandatory, be it by limb
salvage or amputation”.
Parosteal osteogenic sarcomas : No Chemotherapy - if low
grade tumors. If a high grade component – surgery plus
postoperative chemo.
Low grade intramedullary osteosarcoma: The treatment is
essentially similar to parosteal osteosarcoma, requiring only
surgerywithout systemic chemotherapy.
Periosteal osteogenic sarcoma: Neoadjuvant chemo +
surgery(wide margical excision) +chemo postoperative.

12. Secondary osteogenic
sarcoma
Secondary osteogenic sarcoma arises on the background of a
previous bone disorder such as
Paget’s disease,
Bone infarct,
Fibrous dysplasia,
Prior radiation,
Rx similar to high grade tumor.

13. Brief on tumour Definition
Osteosarcoma is defined as a primary malignant tumor in which the
malignant mesenchymal cells produce osteoid and/or immature
bone.
It is the most common primary malignant tumor of bone,
excluding those of hematopoietic origin
• Osteosarcomas can be broadly classified into
1)Intramedullary 2)surface 3)Extraskeletal.
.

14. Cntnue..
Osteosarcomas are divided into high and low grade tumors.
High grade osteosarcomas :
Conventional osteosarcoma, Telangiectatic osteosarcoma, Small
cell osteosarcoma and high grade surface osteosarcomas.
Low grade osteosarcomas : include low grade central and
parosteal
osteosarcoma.
Periosteal chondrogenic type of osteosarcoma is an
Intermediate grade osteosarcoma.

15. Advances in imaging
• (MRI) – detailed assessment of tumor extent within the bone
marrow cavity and into soft tissues and surrounding structures
such as joints, nerves, and vessels.
• Recently , MRI may also be used to predict histologic tumor
response to preoperative chemotherapy,as may positron
emission tomography (PET)/computed tomography (CT),
sequential bone scans, and others. PET/MRI has entered the
scene more recently
• Chest CT remains the gold standard for imaging lung
metastases.

16. Detecting skeletal metastasis:
• In past , 99mTechnetium bone scans have long been part of
thestandard diagnostic workup ,but some years ago whole-
body MRI with short time inversion recovery (STIR) imaging
was found to be more sensitive for detecting bone
metastases in children with suspected multifocal bone lesions
than bone scans, but also less specific.
• Recently ,STIR–MRI or PET/CT >> Bone scans in detecting
skeletal mets but histologic confirmationwith a biopsy is
often required.

17. Advances in biopsy
techniques:
• Traditionally, biopsies were performed via incisional
procedures.
• Recently , Even though -paucity of tissue for research, less
invasive core needle biopsies (CNBs) are now assuming an
ever-increasing role. These have been shown to be very
effective as long as adequate cores can be sampled.

18. What says the Recent study?
• French analysis of CNB in 73 osteosarcomas
reported an overall sensitivity of 93.1%, specificity of
100%, and positive and negative predictive values
of 100% and 99.9%, respectively, as long as the
specimen was adequate. Taupin T, Decouvelaere AV, Vaz G, et
al.: Accuracy of core needle biopsy for the diagnosis of osteosarcoma: A
retrospective analysis of 73 patients.Diagn Interv Imaging. 2016; 97(3): 327–
31.

19. Advances in local therapy of
operable osteosarcoma
• Surgery with wide margins- remains the mainstay
• Recent years have witnessed a major shift from amputations
towards limb-saving procedures.
• Various non-invasive lengthening mechanisms like
incorporated engines or magnetic devices. However, these are
still associated with frequent complications and needs for
revisions.
• Expandable endo-prosthesis require additional surgery for
every lengthening.

20. Advances in local treatment of
inoperable osteosarcomas
• Proton and heavy-ion radiotherapy have come into focus.
• Osteosarcoma of the trunk irradiated with a median of 70.4
Gy carbon-ion radiotherapy (CIRT).
• Permanent local control with radiotherapy, particularly if this
is combined with effective chemotherapy and gross total
resection.
• Results of a meta-analysis suggest that debulking
may no longer be required when radiation doses of
70 Gy or higher are administered. Ciernik IF, Niemierko
A, Harmon DC, et al.: Proton-based radiotherapy
forunresectable or incompletely resected
osteosarcoma. Cancer. 2011; 117(19): 4522–30.

21. Advances in systemic
treatment
• The MAP combination of HD-MTX, doxorubicin,and cisplatin is
frequently used nowdays (New additions to this regimen are
the cytotoxic agent ifosfamide and the macrophage activator
liposomal muramyl tripeptide phosphatidylethanolamine (L-
MTPPE,mifamurtide).
• New drug with immunological properties interferon alpha-2b
added.

22. Advances in surgery :
• Resection :
• Surgical margins are defined as intralesional, marginal, wide,
and radical.
• An intralesional margin is created if the tumor is entered at
any point during surgery.
• A marginal margin is created when the dissection extends into
or through the reactive zone that surrounds the tumor
• A wide margin is created when the reactive zone is not
entered and the entire dissection is performed through
healthy tissues.
• A radical margin is created when the entire bony or
myofascial compartment or compartments containing the
tumor is resected.

23. Old resection vs Recent
resection for osteosarcoma
• Old and usual :
• The principle of surgical resection of osteosarcoma (as for any
sarcoma of bone) is resection with wide margins (removal of
tumor with a cuff of normal tissue covering it all around). This
usually means removal of 2 cm normal tissue or a good
anatomical barrier (e.g fascial layer/articular cartilage) and
osteotomy of bone 3–5 cm away from the level of
involvement

24. Recent recommendation :
• Smaller margins on bone being acceptable for resection after
effective neoadjuvant treatment.
• Joint sparing resections using the open physeal cartilage as
margin are also oncologically sound, while saving the nearby
joint at the same time.
• Computer navigation for accurate resection with safe margin
based on imaging findings while preserving as much bone as
feasible.

25. Reconstruction techniques :
• Common mode : Reconstruction with megaprosthesis is a
common mode of reconstruction as it has a predictable
functional outcome, allows early rehabilitation, allows for
intraoperative flexibility in the length of the reconstruction
required and being non biological, is unaffected by adjuvant
chemotherapy
•

26. Disadvantage of
megaprosthesis ?
• Main disadvantage of megaprosthesis
• The vulnerability to wear and tear leading to
loosening/breakage in the long term.
• Furthermore, the reattachment of tendons to the prosthesis is
another factor compromising the functional outcome.

27. Newer prosthesis
• Availability of expandable prosthesis has minimized the
problem of limb length discrepancy in young children with
significant remaining growth, as they can be lengthened non-
invasively.

28. Improvements in prosthetic
technology
• Improvements in prosthetic technology
1. Rotating platform design,
2. HA coated collar and stem,
3. Porous tantalum and
4. Compression osteointegration technology.

29. Other options :
• External fixators by circular frame (Ilizarov )
• Plate fixation with grafting
• Nailing procedures

30. Biological methods of
reconstruction
• Biological reconstruction may be used for
1. Arthrodesis
2. Intercalary reconstruction
3. osteoarticular graft.

31. Advances in follow-up
• Osteosarcoma recurrences may still be cured as long as they
are operable.
• Surveillance usually includes chest X-rays or chest CTs in
addition to history, physical, and imaging of the former
primary tumor site.
• Chest X-ray was compared withCT scanning and 6-monthly
with 3-monthly follow-up and concluded that chest X-rays
were not inferior to CT scans in terms of detecting pulmonary
metastases and did not lead to inferior survival;
• 3-year overall survival was 64% with 6-monthly and 69% with
3-monthly follow-up, respectively

32. • Currently available evidence shows that routine follow-up for
lung metastases can usually be performed with chest X-rays.
Ultralow-dose CT, which limits radiation exposure to the
equivalent of chest X-rays in two planes, has shown promise
for lung cancer screening.

34. Future outlook
• The optimal “conventional” chemotherapy regimen remains to
be defined, and efforts to identify additional effective
cytotoxic combinations, as exemplified by the demonstration
of activity for the gemcitabine/ docetaxel combination, or to
augment the usability of known effective agents by mitigating
toxicities, exemplified by adding the cardioprotective agent
dexrazoxane to increase doxorubicin exposure.
• The identification of the phosphatidylinositol 3 -
kinase/mammalian target of rapamycin (PI3K/mTOR) pathway
as a central vulnerability for therapeutic exploitation and
subsequent detection of responsiveness of osteosarcoma cell
lines to PI3K/mTOR inhibition.

35. Thank you