OsteosarcomaOsteosarcoma: :
EuramosEuramos StudyStudy
Mark BernsteinMark Bernstein
ChiefChief, Division of , Division of PediatricPediatric OncologyOncology//HematologyHematology
IWK Health Center, Halifax, CanadaIWK Health Center, Halifax, Canada
Trial Management Group Chair, Trial Management Group Chair, EuramosEuramos I I
OsteosarcomaOsteosarcoma: :
EpidemiologyEpidemiology
�� Most Most frequentfrequent primaryprimary tumortumor of of bonebone
�� 5% of 5% of malignantmalignant diseasedisease in in
adolescenceadolescence
�� Male:FemaleMale:Female 3:23:2
�� 450 450 –– 550 cases in 550 cases in NorthNorth AmericaAmerica per per
yearyear underunder 19 19 yearsyears
�� 150150--200 cases in 200 cases in thosethose 2020--29 29 yearsyears of of
ageage
�Similar
RegimensMAP- MAPI
�Similar Results
�Progress Slow
�� SimilarSimilar
RegimensRegimensMAPMAP-- MAPIMAPI
�� SimilarSimilar ResultsResults
�� Progress Progress SlowSlow
OsteosarcomaOsteosarcoma::International StudiesInternational Studies
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Osteosarcoma: 5-year survivalrates
Salvage of Salvage of poor poor
responders ?responders ?
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Osteosarcoma: Response & Survival
good (n=734)
73.4% (SE 2%)
47.2% (SE 3%)
poor (n=586)
p<.0001COSS:Bielacket al 2002
3 year EFS: good ≈≈≈≈ 70%poor ≈≈≈≈ 45%
Significance 5%Power 80%45% ⇒⇒⇒⇒ 55%
Salvage-Question Statistics
SalvageSalvage--Question Question StatisticsStatistics
Osteosarco
ma
Osteosarco
ma
EURAMOSEURAMOS
3 year EFS: good ≈≈≈≈ 70%poor ≈≈≈≈ 45%
Significance 5%Power 80%45% ⇒⇒⇒⇒ 55%
needed: ± 700 poor responders⇒ ±±±± 1400 patients
Salvage-Question Statistics
SalvageSalvage--Question Question StatisticsStatistics
Osteosarco
ma
Osteosarco
ma
EURAMOSEURAMOS
Outcome ImprovementOutcome Improvement
��Good respondersGood responders
�� 70 to 80%70 to 80%
�� Around 600 randomized Around 600 randomized
patientspatients
EuramosEuramos: Study design : Study design
�� Should postShould post--operative therapy be operative therapy be altered based on histological altered based on histological response?response?
�� Choice influenced by toxicity profile of Choice influenced by toxicity profile of medications:medications:
–– IfosfamideIfosfamide, , etoposideetoposide: bone marrow : bone marrow suppression, fever, sterility, induced suppression, fever, sterility, induced leukemia, renal dysfunctionleukemia, renal dysfunction
–– Interferon: fluInterferon: flu--like syndrome; spasticity in like syndrome; spasticity in young children, mainly infants: those less young children, mainly infants: those less than 5 years of age excludedthan 5 years of age excluded
Cisp-Dox-MTX
surgery
Good: CDM
CDM +
pegintron
CDMIE
POOR
R
A
N
D
O
M
I
Z
E
CDM: cisplatin, doxorubicin, high-dose methotrexate
POOR >10% viable tumor
OsteosarcomaOsteosarcoma, , EuramosEuramos
CDMR
A
N
D
O
M
I
Z
E
EURAMOS Recruitment as of August 31,
2008
EURAMOSEURAMOS Recruitment Recruitment as of August 31, as of August 31,
20082008
Courtesy of EURAMOS-CDC,
MRC London
EURAMOS Randomisation as of August
31, 2008
EURAMOSEURAMOS RandomisationRandomisation as of August as of August
31, 200831, 2008
Courtesy of EURAMOS-CDC,
MRC London
EuramosEuramos: Study problems: Study problems
�� Good responder rate higher than Good responder rate higher than predictedpredicted
�� Randomization rate lower than Randomization rate lower than predictedpredicted–– 6565--70%, not 8570%, not 85--90%90%
–– Late, at week 15Late, at week 15--1616
�� Accrual likely to be extended (to June, Accrual likely to be extended (to June, 2010)2010)
FAQsFAQs
�� Is it okay to proceed with my institutional Is it okay to proceed with my institutional
pathologist'sassessmentpathologist'sassessment or do I have to wait or do I have to wait
for Dr. for Dr. TeotTeot??
Answer: It is okay to proceed with your Answer: It is okay to proceed with your
institutional pathologistinstitutional pathologist’’s assessment. S/he s assessment. S/he
is the pathologist of record. Note: is the pathologist of record. Note:
disagreement is relatively uncommondisagreement is relatively uncommon
FAQsFAQs
�� Is it necessary to send specimens to Is it necessary to send specimens to
the BPC for Dr. the BPC for Dr. Teot'sTeot's review if we review if we
decide to proceed with our own decide to proceed with our own
institutional pathologist's assessment?institutional pathologist's assessment?
�� Answer: yesAnswer: yes