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Chou AJ, Merola PR, Vyas Y, Wexler L, Gorlick R, LaQuaglia M, Healey J, Huvos A, Meyers PA

Treatment of Relapsed Osteosarcoma After Contemporary Therapy: The Memorial Sloan-Kettering Experience. Chou AJ, Merola PR, Vyas Y, Wexler L, Gorlick R, LaQuaglia M, Healey J, Huvos A, Meyers PA. Scope of the Problem. > 400 new pediatric cases of OS / year

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Chou AJ, Merola PR, Vyas Y, Wexler L, Gorlick R, LaQuaglia M, Healey J, Huvos A, Meyers PA

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  1. Treatment of Relapsed Osteosarcoma After Contemporary Therapy: The Memorial Sloan-Kettering Experience Chou AJ, Merola PR, Vyas Y, Wexler L, Gorlick R, LaQuaglia M, Healey J, Huvos A, Meyers PA

  2. Scope of the Problem • > 400 new pediatric cases of OS / year • survival for localized disease > 70% • < 20% for recurrent disease • optimal strategy for recurrent disease is undefined

  3. Treatment for Recurrent OS

  4. Study Objective • To determine the outcome for patients with recurrent OS who were treated at MSKCC after 1st relapse (R1)

  5. Study Description • Retrospective chart review • Eligibility criteria: • biopsy proven high grade osteosarcoma • documented CR after receiving “contemporary” therapy = surgery + chemotherapy [HD MTX, CDDP, DOX, + IFOS] • tx for R1 at MSKCC after 1990 • Definitions: • RFS = time from CR2 to either R2 or death from any cause • RFS=0 if never achieved CR2 • Overall-survival = time from 1st relapse to death from any cause • RFI = time from initial diagnosis to 1st relapse

  6. Patient Characteristics • N=43 • Males = 27 (63%) • Females = 16 (37%) • median age at primary Dx = 15 y (4.5 – 31.4) • primary extremity tumors = 38 (88%) • primary axial tumors = 5 (12%) • metastases at primary diagnosis = 10 (23%)

  7. Median time to 1st relapse < 24 months after diagnosis • median time to 1st relapse = 21.7 months (4.6 – 135.7) from primary dx • # achieved CR2 = 26 / 43 (60%)

  8. Lungs are the most common sites of relapse • Sites of relapse • lungs alone = 22 • unilateral = 13 • bilateral = 9 • multiple nodules = 13 • solitary nodules = 9 • local = 6 • bone = 14 • lung + other = 11 • soft tissue (incl. liver) = 3

  9. 35% Crude Overall Survival • Total alive = 15 / 43 (35%)* • Alive with disease = 4 • Alive without disease = 11 • Median Follow-Up after R1 = 15.2 months (0.7-158.3) • Survival at Median Follow-Up after R1 = 26 / 43 (60.5%) *as of July 2004

  10. Proportion Surviving Time (months) Overall Survival from 1st Relapse

  11. Progressive disease is the most common cause of death after 1st relapse • Causes of death: • progressive OS = 23 • sepsis = 2 (1 in CR) • ARDS = 2 (1 in CR) • 2o AML/MDS = 1 (in CR)

  12. RFI > 24 months = 9/17 (53%) Achieving CR2 = 15/26 (58%) Lungs – unilateral = 7/13 (54%) Lungs – solitary = 5/9 (56%) RFI < 24 months = 6/26 (23%)* Not achieving CR2 = 0/17 (0%)* Lungs – bilateral = 2/9 (22%) Lungs – multiple = 4/13 (31%) Survival correlated with RFI > 24 months and achievement of CR2 *p<0 .05

  13. Treatment Strategies for R1 • Surgery alone = 4 • 2/4 relapsed after CR2 • overall survival = 3/4 • Chemotherapy alone = 7 • overall survival = 0/7 • Chemotherapy + Surgery = 32 • For those +CR2, 11/22 relapsed • overall survival = 12/32

  14. Ifosfamide / Etoposide Cisplatin / Doxorubicin HD Methotrexate HD Cyclophosphamide Irinotecan Gemcitabine + Docetaxel Mitoxantrone Cyclophosphamide / Topotecan Carboplatin 5-Flourouracil Thioguanine Other agents (trimetrexate, ET-743, STI571, trastuzumab, Dx-8951f, interferon/VP16, Gm-CSF) Multiple chemotherapeutic strategies were utilized in 1st relapse

  15. Chemo + Surg (n=32): Overall Survival since R1

  16. Chemo + Surg (n=32): Relapse Free Survival since R1

  17. For Chemo + Surg: regimens +IFOS confer advantage in preventing 2nd relapse • 23 patients received IFOS as part of R1 treatment • CR2 = 18 • R2 = 8 • 9 patients did not receive IFOS as part of R1 treatment • CR2 = 4 • R2=3

  18. =+Ifos =-Ifos +IFOS (n=23) vs. -IFOS (n=9) regimens: Relapse Free Survival after R1

  19. =HD Ifos =other HD IFOS (n=22) vs. all other chemo regimens (n=10): Overall Survival after R1

  20. Conclusions • Chemotherapy with curative-intent surgery can successfully salvage 22/32 of patients at 1st relapse  9/32 remain NED. • Chemotherapy regimens containing ifosfamide appear to confer an advantage in preventing a 2nd relapse.

  21. Paul A. Meyers, MD Pediatric Sarcoma Team Leonard H. Wexler, MD Richard Gorlick, MD Pamela R. Merola, MD Yatin Vyas, MD Karen Allison, CPNP Jamie Viccola, CPNP Stephanie Vitolano, CPNP Surgical Team Michael P. LaQuaglia, MD John H. Healey, MD Andrew G. Huvos, MD

  22. =IFOS naive =IFOS exposed DFS For HD IFOS group: IFOS naïve (n=19) vs. IFOS exposed (n=3)

  23. =chemo + surg =surg Proportion Surviving Time (months) Comparison of DFS From Hawkins et al, Cancer 2003

  24. Proportion Surviving Time (months) Comparison of Overall Survival From Hawkins et al, Cancer 2003

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