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

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Soft Tissue Sarcomas

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