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Medical oncology > Bony Sarcomas > Flashcards

Bony Sarcomas Flashcards

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USMLE® Step 1 flashcards
1
Q

What is the distribution of osteosarcoma?

A

8% mandible
10% humerus
15% hip/femur
60% knee

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2
Q

What is identified on the pathology of osteosarcoma?

A

Malignant osteoblasts and osteoid
Pink amorphous intercellular material
+/- Collagen (Complix Dx)

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3
Q

What are the Primary osteosarcoma subtypes?

A

G.P. CTSP

Grade
- Low Grade central
- High Grade surface
Periosteal

Conventional
- Osteoblastic
- chondroblastic
- Fibroblastic
Telengiectatic
Small Cell
Paraosteal
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4
Q

Is osteosarcoma radiation sensitive?

A

NO

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5
Q

What are the surgical options for osteosarcoma?

A

1) Amputation
2) Wide excision +/- megaprosthesis
3) Rotationplasty

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6
Q

What is the survival rate of osteosarcoma with surgery alone?

A

20%

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7
Q

What are the more recent historical trials showing benefit of adjuvant chemotherapy

A

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

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8
Q

What are the theoretical advantages of pre-op chemo?

A

S.P.O.R.T

Salvage of limb
Prosthesis modeling
O -micrO-met management 
Response to chemo for prognostication
Tailor post-op treatment
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9
Q

Tell me about POG-8651 study

A

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
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10
Q

What prognostic factors of osteosarcoma do you know?

A

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

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11
Q

Tell me briefly about the EOI studies

A

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

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12
Q

Tell me about EOI-1

A

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

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13
Q

Tell me about EOI-2

A

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%
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14
Q

Tell me about EOI-3

A

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]

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15
Q

What s the conclusion of EOI 1/2/3?

A

Standard of care in Europe is:

1) Doxo (75) + CDDP (100)
2) Q3w dosing
3) 6 cycles
4) 3# before surgery, 3# after surgery

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16
Q

What do you know about the COG MAP protocol?

A

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

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17
Q

Tell me about the EURAMOS 1

A

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]

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18
Q

Tell me what you know about Muramyl Tripeptide

A

MTP = Muramyl Tripeptide

Immune stimulant
Component of BCG Cell wall

Delivered to monocytes + Macrophages and becomes activated.
When activated, becomes tumoricidal

19
Q

Any RCTs that you know about that used Muramyl Tripeptide?

A

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

20
Q

What percentage of patients with 1st osteosarcoma relapse are long-term survivors?

A

15-20%

Remaining:
1/2 do not achieve CR
1/2 achieve CR and relapse further

21
Q

What is the 5y OS for 5th Recurrence of osteosarcoma?

A

20%

22
Q

What are the risk factors for osteosarcoma so?

A

Previous RT
Pages disease of bone
Germline abnormalities (eg Li-Fraumeni, Werner, Rothmund-Thomson, loom, Hereditary retinoblastoma)

23
Q

What is the most common bony sarcoma of adulthood?

A

Chondrosarcoma

24
Q

What is the most likely bone tumor in the following age groups:
(A) 5 yo
(C) >40yo

A

(A) 5 yo
- Primary bone sarcoma

(C) >40yo

  • metastasis
  • myeloma
25
Q

Why is internal fixation contraindicated in a case of pathological fracture when bony tumors are suspected?

A

This will result in dissemination of tumor further into the bone and soft tissue, and will increase the risk of local recurrence.

External splintage is recommended + adequate pain control

26
Q

Which part of the bone does osteosarcoma usually arise from?

A

Metaphysis of a long bone

Most commonly around the knee.

27
Q

What are the adverse prognostic or predictive factors of osteosarcoma?

A 
Detectable primary mets
Axial or proximal extremity tumor site 
Large tumor size 
Elevated serum ALP or LDH
Older age
28
Q

Which osteosarcomas have a lower metastatic potential?

A

Low-grade central osteosarcoma

Paraosteal osteosarcoma

29
Q

Describe the molecular biology of Ewing sarcoma

A

Almost all share a common gene rearrangement involving:
- reciprocal translocation t(11;22)(q24;q12)

Other translocation so include:

  • t(21;22)(q22;q12)
  • t(7;22)
  • t(17;22)
  • t(2;22)
  • inv (22)
30
Q

What are the 6 most active chemotherapeutic agents in the treatment of Ewing’s sarcoma?

A 
Cyclophosphamide
Doxorubicin
Vincristine
Ifosfamide
Etoposide
Dactinomycin
31
Q

What are the types of chondrosarcoma that you know of?

A

1) Intramedullary
- Conventional (Hyaline/myxoid)
- cc
- De-differentiated
- Mesenchymal
2) Juxtacortical

32
Q

What is condrosarcoma?

A

Rare bone sarcoma

Characterized by the production of cartilage by neoplastic cells

5 main types:

1) Conventional
- Primary central chondrosarcoma
- secondary peripheral chondrosarcoma
2) cc
3) De-differentiated
4) Mesenchymal

33
Q

What is the general treatment outline for chondrosarcoma?

A

Relatively chemo and radio-resistant

Conventional/cc = surgery
De-differentiated = treat as for Osteosarcoma with Adjuvant AP
Mesenchymal - treat as for Ewing’s

34
Q

What is the general treatment outline for Ewing’s sarcoma?

A

Induction chemo - 4 to 6 cycles
Local therapy - Surgery vs radiation
Adjuvant chemo - total 14#

Choice of chemo - Alternating CAV-IE

Grier NEJM 2003

35
Q

What is the evidence for CAV-IE in the treatment of Ewing’s sarcoma and primitive neuroectodermal tumor of bone?

A

NCI protocol INT-0091
Grier NEJM 2003

30 yo or younger, n=500
2 arms:
1) 49w of CAV alone
2) CAV alternating with IE

Chemo Q3weekly X 17 courses = 49 weeks
Dactinomycin substituted for Doxorubcin when dose >375mg/m2

RESULTS:
5y EFS 55% vs 70%
5y OS 60% vs 70%

36
Q

What is the evidence for using did CAV-IE in Ewing’s ?

A

Womer JCO 2008

Sensitivity of ESFT (Ewing sarcoma family tumors) to alkylating agents with a steep dose response curve

37
Q

List in order of most frequent to least frequent:

Chondrosarcoma, osteosarcoma, Ewing’s

A

1) Osteosarcoma

- 55%

38
Q

Tell me about the COSS study

A

Cooperative Osteosarcoma Study Group (COSS) analysis

1700 patients
Time to relapse 18m, with subsequent relapses shorter
1st relapse usually distant (87%), of which 3/4 lung only

1st Osteosarcoma relapse:

  • 20% are long-term survivors
  • 40% achieve CR and relapse further
  • 40% never achieve CR
39
Q

What is Giant Cell Tumor?

A

Aggressive, locally recurrent tumor of low malignant potential

Histo; unknown origin
Sites: Long bone, vertebra, sacrum

20% become malignant after local recurrence

Resection provides 90% cure
Currettage provides 50% recurrence

Adjuvant RT has a role as:

  • GCT is radio-sensitive
  • local control rate 80%
  • consider for Unresectable cases
40
Q

Which part of the bone does chondrosarcoma usually arise from?

A

Metaphyseal region of long bones

41
Q

Where do Chordoma arise from?

A

From embryonic remnants of the notochord

More common in older adults

42
Q

Where are chordomas found?

A

Axial skeleton
Skull base
Sacrum
Spine

43
Q

What makes up the Ewing’s Sarcoma Family of Tumors? (ESFTs)

A

ESFTs are a group of small round-cell neoplasms.

They include:

1) Ewing’ sarcoma
2) PNET (Primitive neuroectodermal tumor)
3) Askin’s tumor
4) PNET of bone
5) Extra-osseous Ewing’s sarcoma

44
Q

What characterizes Ewing’s

A

Fusion of EWS gene with various members of the ETS gene family

EWS gene = EWSR1 
- on chromosome 22q12 
ETS Gene family include:
- FLI1
- ERG
- ETV1
- ETV4
- FEV

EWS-FLI1 fusion transcript results from fusion of EWS and FLI1

  • FLI1 is located on chromosome 11
  • t(11;22)(q24;12)
  • identified in 85% of pts Ewing’s

Ewing’s is also characterized by strong expression of cell surface glycoproteins MIC2 (CD99)

Medical oncology (53 decks)

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