Clinicopathologic Features of Diaphyseal Osteosarcoma Anne N. Normand, MD Patrick P. Lin, MD Norman...
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Transcript of Clinicopathologic Features of Diaphyseal Osteosarcoma Anne N. Normand, MD Patrick P. Lin, MD Norman...
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Clinicopathologic Features of Diaphyseal Osteosarcoma
Anne N. Normand, MDPatrick P. Lin, MDNorman Jaffe, MDRobert S. Benjamin, MD Shreyaskumar R . Patel, MDChristopher P. Cannon, MDValerae O. Lewis, MDA. Kevin Raymond, MDAlan W. Yasko, MD, MBA
CTOS Meeting
November 2005
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High-grade intramedullary osteosarcoma
• Most common in metaphyseal region of long bones
• Rare in the diaphyseal region– Previously reported to occur <10% of cases– Site of osteosarcoma variants (eg, periosteal,
high-grade surface OS)
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Bone: Structural Differences
• Metaphysis– Many trabeculae
– Thin cortices
– Rich vascular supply
– Vascular sinusoids
– Large surface area exposed to circulation
– Extensive remodeling, growth
• Diaphysis– Fewer trabeculae
– Thick lamellar cortical bone
– Nutrient artery & periosteum
– Diffusion
– Slower bone turnover
– Slower healing
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Literature
• Sim et al, 1995 – Mayo Clinic
– 51 cases
– 1912-1979
– ~7% of all long bone OS treated during that period
– No chemotherapy protocols
– 73% (38/51) no chemo
– 5-year survival 29%
• Haworth et al, 1981– Bristol Royal Infirmary
– Radiographic review
– Heterogeneous presentation, broad DDx
– 5-year survival 23%
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Hypothesis
• Diaphyseal and metaphyseal bone differ anatomically and metabolically.
– Clinicopathologic features of tumors may differ
– Response to treatment may differ
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Purpose
• Describe clinicopathologic features of diaphyseal osteosarcoma
• Determine differences in outcome between diaphyseal and metaphyseal osteosarcoma with contemporary treatment
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Materials & Methods
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Study Design
• Retrospective review
• High-grade intramedullary OS of long bones
• 1980 to 1999
• 5-year potential follow-up
• 51 diaphyseal, 240 metaphyseal
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Exclusion criteria
• Surface OS
• Low- and intermediate-grade OS
• Secondary OS
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Definition: Diaphyseal OS
• Epicenter within the area between parallel cortices– Radiographic
– Pathologic
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Treatment algorithm
• Pre-operative chemotherapy - 4 cycles
• Surgical treatment
• Post-operative chemotherapy - tailored– Good responders (≥90%)
– Poor responders (<90%)
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Pre-op chemotherapy
• Intra-arterial cis-platin (120 mg/m2)
• Intravenous doxorubicin (90 mg/m2)
• 4 cycles
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Surgical treatment
Diaphyseal Metaphyseal
Amputation 12 42
Limb-salvage
39 198
p = 0.321
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Post-operative chemotherapy
• Good responders - short course– IV cis-platin– IV doxorubicin
• Poor responders - extended course– High-dose methotrexate (12.5 g/m2)– High-dose ifosfamide (14 g/m2)
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Statistics
• Kaplan-Meier analysis– Disease-specific survival – Log rank test
• Chi-square test
• Independent student’s t test
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Results
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DemographicsDiaphyseal Metaphyseal p
Number 51 240
Age (yrs)
Mean
Range
22
4-72
19
4-75
0.286
Gender
Male
Female
31 (61%)
20 (39%)
141 (59%)
99 (41%)
0.869
F/u (mo.)
Mean
Range
106
3-288
99
1-283
0.177
Stage
Non-metas
Metastatic
48 (94%)
3 (6%)
225 (94%)
15 (6%)
0.916
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Affected sites
p=0.339
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Presentation
• Symptoms – Pain most common
– Local swelling, mass
• Pathologic fracture– Diaphyseal 9/51 (18%)
– Metaphyseal 39/240 (16%)
– p = 0.657
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Radiographic presentation
Lytic Mixed Blastic
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Histology
Metaphyseal
TELANGIECTATIC
SMALL CELL
OSTEOBLASTIC
MIXED
FIBROBLASTIC
CHONDROBLASTIC
Diaphyseal
TELANGIECTATIC
SMALL CELL
OSTEOBLASTIC
MIXED
FIBROBLASTIC
CHONDROBLASTIC
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Tumor necrosis
Diaphysis Metaphysis
Good 16 134
Poor 32 96
p = 0.0016
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Disease-specific survival
Follow-up (months) (p=0.499)
300240180120600
DSS
1.0
.8
.6
.4
.2
0.0
Metaphyseal
Diaphyseal
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Disease-specific survival
Diaphyseal Metaphyseal
5 years 62% 69%
10 years 59% 60%
20 years 56% 60%
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DSS & Tumor Necrosis
Follow-up (months)
300240180120600
DSS - Tumor necrosis >90%
1.0
.8
.6
.4
.2
0.0
Metaphyseal
Diaphyseal
Follow-up (months)
300240180120600
DSS - Tumor necrosis <90%
1.0
.8
.6
.4
.2
0.0
Metaphyseal
Diaphyseal
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Impact of metastatic disease
Follow-up (months) (p=0.21)
300240180120600
DSS - Metastatic disease
1.0
.8
.6
.4
.2
0.0
MetaphysealDiaphyseal
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Discussion
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Similarities
• Diaphyseal & metaphyseal OS share many features– Age– Gender– Sites– Presentation– Histological subtypes
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Key Difference Response to pre-op chemotherapy
• Diaphyseal OS less sensitive than metaphyseal OS to doxorubicin & IA-cisplatin
– ?Anatomical/vascular/structural differences
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Similar outcomes
• Disease-specific survival same
• Supports tailoring of post-op chemotherapy– Switch to HD-MTX & HD-IFX– Historical data
• survival w/ poor response to pre-op chemo significantly worse
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Conclusion
• Clinicopathological characteristics of diaphyseal OS are similar to metaphyseal OS
• Diaphyseal OS responds less well to pre-op chemo
• Tailoring of post-op chemo for poor responders to include HD-MTX & HD-IFX may be important to achieve good survival
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Thank you