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Neoadjuvant Chemotherapy in Malignant Peripheral Nerve Sheath Tumors

Neoadjuvant Chemotherapy in Malignant Peripheral Nerve Sheath Tumors. Elizabeth Shurell, M.D., M.Phil. UCLA General Surgery Resident Research Fellow, Division of Surgical Oncology. Disclosures. I have no financial disclosures or other relationships relevant to this research. Background.

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Neoadjuvant Chemotherapy in Malignant Peripheral Nerve Sheath Tumors

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  1. Neoadjuvant Chemotherapy in Malignant Peripheral Nerve Sheath Tumors Elizabeth Shurell, M.D., M.Phil. UCLA General Surgery Resident Research Fellow, Division of Surgical Oncology

  2. Disclosures I have no financial disclosures or other relationships relevant to this research.

  3. Background MPNST Characteristics • Neurofibromatosis type 1 (NF-1) • Lifetime risk 10% • General Population • Lifetime risk < 0.01% • Poor prognosis, frequent metastases and few treatment options MFH Other FibrosarcomaLipoLeiomyo Synovial MPNST Increasing sarcoma-specific mortality Figure adapted from: Kattan, Leung, and Brennan. J ClinOnc, 2002.

  4. Background Imatinib Crizotinib Taxanes Imatinib Trabectedin Pazopanib Sunitinib Cediranib Pazopanib Taylor et al. Nature Reviews Cancer 2011.

  5. Background Therapy for MPNST • Response rate of MPNSTs to standard chemotherapy is unknown • Kroep et al, Leiden University Medical Center (2010) • n=175 unresectable/metastatic pts; combination adriamycin/ifosfamide yielded best response: 1 year progression free survival: 25% • Moretti et al, U of Pennsylvania (2011) • n=10 (4 pts metastatic); combination adriamycin/ifosfamide yielded 57% DFS and 80% OS at 2 years

  6. Background Neoadjuvant Therapy for MPNST OneMPNST clinical trial: Phase II trial of neoadjuvant chemotherapy in sporadic and NF1 associated high grade unresectable MPNST (NCT00346164) (open, not actively recruiting)

  7. Background Roles of Neoadjuvant Therapy • Cytoreduction, downstaging • Decrease micro-metastatic disease • Reducing consequences of a more extensive surgery • Tool to determine patient sensitivity to chemotherapy

  8. Background Objective What we know: Grade, Size, and Location are the most important predictors of survival in MPNST patients. Goal: Evaluate pathologic response of neoadjuvant chemotherapy in primary MPNST patients and its impact on survival.

  9. Methods Methods for analysis • Primary outcomes: Disease specific survival, Disease free survival • The a priori chosen prognostic covariates were: • Age (modeled as continuous covariate) • Sex (male, female) • Presence of Neurofibromatosis type 1 (NF1) • Tumor size (modeled as continuous covariate) • Grade (low, intermediate, high) • Location (Retroperitoneal, Extremity, Trunk, etc) • Margin status (microscopically negative, microscopically positive) • Neoadjuvant XRT (yes, no) • Type of neoadjuvant chemotherapy (non-ifosfamide versus ifosfamide-based)

  10. Results Neoadjuvant Chemotherapy n=38

  11. Results Neoadjuvant Chemotherapy 90% pathologic response Non-Responders n=25 (66%) Responders n=13 (34%) n=38

  12. Results Characteristics p=0.032

  13. Results Survival Analysis Harrell’s C = 0.72 Harrell’s C = 0.75 DSS = Disease Specific Survival; DFS = Disease Free Survival

  14. Results Overall Disease Free Survival n=38 primary MPNST patients treated with neoadjuvant chemotherapy Survival Proportions 2 year 5 year 10 year 60.5% 51.8% 39.6%

  15. Results Pathologic response rate correlates with disease free survival

  16. Results Overall Disease Specific Survival n=38 primary MPNST patients treated with neoadjuvant chemotherapy Survival Proportions 2 year 5 year 10 year 68.4% 62.9% 48.0%

  17. Results Pathologic response rate correlates with disease specific survival

  18. Conclusion Conclusions of clinical study • Our pathologic response rate was 34%, and is associated with significant improvement in both DSS and DFS in primary MPNST • Future challenge: to determine upfront which patients will be “responders” to standard systemic therapy

  19. Thank you! Acknowledgements UCLA Sarcoma Program Dr. Fritz C. Eilber Dr. Frederick R. Eilber Dr. Sarah Dry Dr. Jeffrey Eckardt Dr. Arun Singh Dr. Noah Federman Dr. Michael Selch Dr. Scott Nelson Dr. William Tap (MSKCC)

  20. Results Pathologic response rate correlates with disease free survival: 95% necrosis _

  21. Results Pathologic response rate correlates with disease specific survival: 95% necrosis _

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