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Soft Tissue Sarcomas in Adolescents and Young Adults   Alberto S. Pappo, M.D. St Jude Children’s Research Hospital Memphis, TN
Childhood Soft Tissue Sarcomas 7% RMS NRSTS
Relative frequency of common cancer types in 15-39 yr olds 1992-2002 (Bleyer Nat Cancer Rev april 2008)
Histologic subtypes of STS by age group
RMS vs NRSTS NRSTS Age > 10 Extremities Resected (70%) Many histologic types Chemorresistant Unproven benefit of adjuvant therapy  Metastases: lung; other sites are rare RX:If/Dox; Targeted therapies RMS Age < 10 HN Unresected (50%) Two histologic types Chemosensitive Adjuvant therapy is effective Metastases: lung, bone, bone marrow Rx: Risk based-VAC
Classification of sarcomas SpecificVariable
Classification of sarcomas
Rhabdomyosarcoma Most common pediatric STS  Heterogeneous, poor survival Collaboration in 1972  CCSG CALGB SWOG   Over 4800 patients treated in 4 consecutive trials IRS (STS-COG)
Survival in RhabdomyosarcomaThree Decades of Progress IRS-IV IRS-III IRS-II IRS-I Pre Cooperative Group
Histologic Subtypes of RMS Embryonal Alveolar
Fusion positive vs Fusion negative ARMS
Risk-Assignment in RMS Low: ~ 35% of RMS Favorable histology, site and lower Group/stage Intermediate: ~ 50% Non met  ARMS Embryonalunresected and met < 10 yr  High: ~ 15% of RMS Remaining metastatic disease 1.0 Low 0.8 Intermediate 0.6 Proportion FFS 0.4 High 0.2 0.0 8 10 0 2 4 6 Years
Intermediate Risk RMS FFS for patients with intermediate risk RMS has not improved 1.0 0.9 IRS-III (1984-1991) 0.8 0.7 IRS-IV (1991-1997) 0.6 Failure-Free Survival 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 Years
Survival of Patients with Metastatic RMS  in IRS-III, IRS-IVP, and IRS IV (1984-1997) 1.0 0.9 0.8 0.7 0.6  Survival 0.5 0.4 IRS-III IRS-IVP 0.3 IRS-IV 0.2 p=0.61 0.1 0.0 0 1 2 3 4 5  Time
Incidence and survival of RMS 1975-2005
Outcome of adult RMS
Estimated % of pts with STS and bone sarcomas enrolled on clinical trials by age 1997-2002 Cancer 103:1891, 2005
Average annual change in 5 yr survival compared to accrual on national trails  1997-2002
Intermediate Risk RMS FFS for patients with intermediate risk RMS has not improved 1.0 0.9 IRS-III (1984-1991) 0.8 0.7 IRS-IV (1991-1997) 0.6 Failure-Free Survival 0.5 0.4 D 9803 7% > 18 yrs 0.3 0.2 0.1 0.0 0 1 2 3 4 5 Years
NRSTS
Incidence of RMS and NRSTS Differs by Age Group SEER Program 1975-1995, NCI
NRSTS Histologic Subtypes J Pediatr Surg 35:948, 2000
IFS with KMS
Infantile HPC
Pediatric GIST
Mutational status 7/65 (11%) KIT or PDGFR mutation- 6/7 males  Kit exons 11 and 9  3/7 PDGFR
KIT mutant GIST Pediatric WT GIST IGF1R Actin
Synovial sarcoma survival
ARST 0332
NRSTS: “not chemo-sensitive”
ARST0332 ,[object Object]
5 yr
306 pts
Accrual on target
7% > 20 yr,[object Object]
Increasing cure rates and “shrinking populations”
How will we design new studies?
The biospecimen “gap”Tumor bank specimens vs. incidence of cancer as a function of patient age
Combination therapy-why and which agents? One year, Dr. Flaherty thought, when he heard the news. Certainly no triumph. But it was something. Something to be built on. ''We just need,'' Dr. Flaherty said, ''to find the right combination.''
“The list”
The Combinations Problem in Cancer: Rhabdo as an example
Incorporation of targeted therapies will improve the outcome of rhabdomyosarcoma: ARST08P1 - PI Suman Malempati * * * * * * Dexrazoxane with all Doxorubicin cycles # IMC-A12 held during XRT (Pilots 1 and 3)
SARC 011 (R1507) trial 12/2007-8/09 111 eligible patients Age: 9-78 (median 26)  20% ≤ 18 yr 73 M; 81 W Bone (n=60) Primary (n=67); Secondary (n=44)

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Soft Tissue Sarcomas