Soft Tissue Sarcomas

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Alberto Pappo, MD, St. Jude Children’s Hospital, Memphis TN …

Alberto Pappo, MD, St. Jude Children’s Hospital, Memphis TN

Presented at the 2010 Texas Adolescent and Young Adult Oncology Conference hosted by Methodist Healthcare-San Antonio. October 2010.

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  • 1. Soft Tissue Sarcomas in Adolescents and Young Adults
    Alberto S. Pappo, M.D.
    St Jude Children’s Research Hospital
    Memphis, TN
  • 2. Childhood Soft Tissue Sarcomas
    7%
    RMS
    NRSTS
  • 3. Relative frequency of common cancer types in 15-39 yr olds 1992-2002 (Bleyer Nat Cancer Rev april 2008)
  • 4.
  • 5.
  • 6. Histologic subtypes of STS by age group
  • 7.
  • 8. 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
  • 9. Classification of sarcomas
    SpecificVariable
  • 10. Classification of sarcomas
  • 11. 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)
  • 12. Survival in RhabdomyosarcomaThree Decades of Progress
    IRS-IV
    IRS-III
    IRS-II
    IRS-I
    Pre
    Cooperative
    Group
  • 13. Histologic Subtypes of RMS
    Embryonal
    Alveolar
  • 14. Fusion positive vs Fusion negative ARMS
  • 15. 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
  • 16. 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
  • 17. 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
  • 18.
  • 19. Incidence and survival of RMS 1975-2005
  • 20. Outcome of adult RMS
  • 21. Estimated % of pts with STS and bone sarcomas enrolled on clinical trials by age 1997-2002
    Cancer 103:1891, 2005
  • 22. Average annual change in 5 yr survival compared to accrual on national trails
    1997-2002
  • 23.
  • 24. 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
  • 25. NRSTS
  • 26. Incidence of RMS and NRSTS Differs by Age Group
    SEER Program 1975-1995, NCI
  • 27. NRSTS Histologic Subtypes
    J Pediatr Surg 35:948, 2000
  • 28. IFS with KMS
  • 29. Infantile HPC
  • 30. Pediatric GIST
  • 31. Mutational status
    7/65 (11%) KIT or PDGFR mutation-
    6/7 males
    Kit exons 11 and 9
    3/7 PDGFR
  • 32. KIT mutant GIST
    Pediatric WT GIST
    IGF1R
    Actin
  • 33.
  • 34. Synovial sarcoma survival
  • 35. ARST 0332
  • 36. NRSTS: “not chemo-sensitive”
  • 37. ARST0332
  • Sarcomas comprise many diseases and molecular genotypes
    Rhabdomyosarcoma
    Embryonal
    Alveolar
    FGFR4 mutated
  • 42. Increasing cure rates and “shrinking populations”
  • 43. How will we design new studies?
  • 44. The biospecimen “gap”Tumor bank specimens vs. incidence of cancer as a function of patient age
  • 45. 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.''
  • 46. “The list”
  • 47. The Combinations Problem in Cancer: Rhabdo as an example
  • 48. 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)
  • 49.
  • 50. 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)
  • 51. Best Recorded Variation in Tumor Size: Ewing’s Cohorts
  • 52.
  • 53. Conclusions
    STS account for 7-8% of cancers in AYA
    Clinical trial enrollment suboptimal
    Sample acquisition suboptimal
    Progress stalled
    Cooperation between adult and pediatric groups essential
    Consortia to study specific diseases