Bony Sarcomas Flashcards
(44 cards)
What is the distribution of osteosarcoma?
8% mandible
10% humerus
15% hip/femur
60% knee
What is identified on the pathology of osteosarcoma?
Malignant osteoblasts and osteoid
Pink amorphous intercellular material
+/- Collagen (Complix Dx)
What are the Primary osteosarcoma subtypes?
G.P. CTSP
Grade
- Low Grade central
- High Grade surface
Periosteal
Conventional - Osteoblastic - chondroblastic - Fibroblastic Telengiectatic Small Cell Paraosteal
Is osteosarcoma radiation sensitive?
NO
What are the surgical options for osteosarcoma?
1) Amputation
2) Wide excision +/- megaprosthesis
3) Rotationplasty
What is the survival rate of osteosarcoma with surgery alone?
20%
What are the more recent historical trials showing benefit of adjuvant chemotherapy
1) Link et al NEJM 1986
- 2y RFS 20% (observation) vs 65% (Adj chemo)
2) Eliber et al
- 2y RFS 20% vs 55% (Adj chemo)
- 2y OS 50% vs 80% (adj chemo)
* Adj chemo used = HD MTX, Doxorubicin, Bleomycin, Cyclophosphamide, Dactinomycin
What are the theoretical advantages of pre-op chemo?
S.P.O.R.T
Salvage of limb Prosthesis modeling O -micrO-met management Response to chemo for prognostication Tailor post-op treatment
Tell me about POG-8651 study
Goorin JCO 2003
Aim: Comparing pre-op chemo vs postop chemo in non metastatic osteosarcoma
N=100
Surgery
RESULTS: 5y EFS: - preop = 60% - postop = 70% [trend] 5y OS: - preop = 76% - postop = 79% [trend] Limb salvage: - preop = 50% - postop = 55% Risk of PD during chemo 13%
Criticisms:
- low rate of limb-sparing surgery in both groups
- inclusion of BCD
What prognostic factors of osteosarcoma do you know?
H.H.E.A.L
1) Histological response
- Good vs poor responders
» Good LTS 80%, Poor LTS 50%
- PD during induction chemo do the worst. ~10%
2) Histo Subtype (COFT)
- Chondroblastic
Tell me briefly about the EOI studies
EOI = European Osteosarcoma Intergroup
EOI-1 = Randomized Phase II exploring benefits of HD MTX + AP
EOI-2 = Standard AP vs T-10 protocol
EOI-3 = Standard 3-weekly AP vs 2-weekly interval
Tell me about EOI-1
Bramwell JCO 1992
Aim: investigating benefits of adding HD MTX to AP
N=200, classical HG osteosarcoma
2 arms:
1) 6# Doxo (75) + CDDP (100) Q3w
2) 4# HD MTX (8g/m2) –> 6# Doxo (75) + CDDP (100)
- HD MTX given 10 days before AP
EOI-1 had surgery sandwiched inbetween
3#AP/2# HDMTX –> Surgery –> 3# AP/2# HDMTX
RESULTS:
5y DFS 60% (AP) vs 40% (MAP) [sig]
5y OS 65% vs 50% (MAP) [not sig]
CONCLUSION:
- no added benefit to HD MTX
Tell me about EOI-2
Link and Eliber
N=400
Operable, non-metastatic osteosarcoma
2 arms:
1) AP
2) T-10
T-10 protocol, alternating chemo
- HD MTX (8-12 g/m2)
- Doxorubicin (30mg/m2/day)
- Bleomycin (15 mg/m2/day)
- Cyclophosphamide (600 mg/m2/day)
- Dactinomycin (600 mcg/m2/day)
In the T-10 protocol, resection/amputation to be done ~4 weeks, after 4 doses of HDMTX
- Endoprosthetic replacement to be done ~16 weeks
RESULTS: 5y PFS 40% 3y OS 65% 5y OS 55% Path CR 30%
Tell me about EOI-3
Aim: To evaluate if there is benefit in intensifying AP by giving it 2-weekly instead of 3-weekly
N=500
2 arms:
1) 6# AP Q3w
2) 6# AP Q2w
Surgery to be done Week 6 in both arms
RESULTS:
Good histo response (I.e.>90% necrosis): 35% vs 50% (q2w)
OS HR 0.94 [trend]
PFS HR 0.98 [trend]
What s the conclusion of EOI 1/2/3?
Standard of care in Europe is:
1) Doxo (75) + CDDP (100)
2) Q3w dosing
3) 6 cycles
4) 3# before surgery, 3# after surgery
What do you know about the COG MAP protocol?
Uses:
- Doxorubicin (75)
- CDDP (120)
- MTX (12g/m2) - max dose 20 mg
Surgery to be done week 10 after 2# of MAP Week 0 AP Week 3 M Week 4 M Q5weekly No break in between except surgery week 10, rest week 11 Resume week 12: AP Week 15 M Week 16 M Week 17 AP
Total 31 weeks
Tell me about the EURAMOS 1
Aim:
1) To evaluate the role of Alpha IFN in good responders
2) To evaluate the role of IE in poor responders
Biopsy-proven resectable osteosarcoma
N=2200
Treated with induction MAP, followed by surgery
We then assess the histology and divide into 2 arms:
1) Good responders
2) Poor responders
Good responders further randomize to:
1) MAP
2) MAP + alpha IFN
Poor responders further randomize to:
1) MAP
2) MAP + IE
====================
Good responders:
Result reported 2015 June JCO, not statistically different from MAP
- 3y EFS 74% (MAP) vs 77% (MAP-IFN) [trend]
Tell me what you know about Muramyl Tripeptide
MTP = Muramyl Tripeptide
Immune stimulant
Component of BCG Cell wall
Delivered to monocytes + Macrophages and becomes activated.
When activated, becomes tumoricidal
Any RCTs that you know about that used Muramyl Tripeptide?
Yes, Meyers JCO 2005
N=650
Prospective phase III study
Newly Dx osteosarcoma
Aim: evaluate benefit of Ifosfamide and/or MTP when added to MAP
4 arm study:
1) MAP + Ifosfamide –> Sx –> Maintenance MAP
2) MAP + MTP –> Sx –> Maintenance MAP/MTP
3) MA + Ifosfamide –> Sx–> Maintenance MD/Ifosfamide/CDDP
4) MA + Ifosfamide + MTP –> Surgery –> Maintenance MAP/Ifosfamide/MTP
RESULTS:
- MTP Trend towards better EFS HR 0.8
- MTP Improves OS HR 0.71
CONCLUSION: No benefit to addition of IE
What percentage of patients with 1st osteosarcoma relapse are long-term survivors?
15-20%
Remaining:
1/2 do not achieve CR
1/2 achieve CR and relapse further
What is the 5y OS for 5th Recurrence of osteosarcoma?
20%
What are the risk factors for osteosarcoma so?
Previous RT
Pages disease of bone
Germline abnormalities (eg Li-Fraumeni, Werner, Rothmund-Thomson, loom, Hereditary retinoblastoma)
What is the most common bony sarcoma of adulthood?
Chondrosarcoma
What is the most likely bone tumor in the following age groups:
(A) 5 yo
(C) >40yo
(A) 5 yo
- Primary bone sarcoma
(C) >40yo
- metastasis
- myeloma
