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

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Presentation on theme: "Neoadjuvant Chemotherapy in Malignant Peripheral Nerve Sheath Tumors Elizabeth Shurell, M.D., M.Phil. UCLA General Surgery Resident Research Fellow, Division."— Presentation transcript:

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 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 Fibrosarcoma Lipo Leiomyo Synovial MPNST Increasing sarcoma-specific mortality Figure adapted from: Kattan, Leung, and Brennan. J Clin Onc, Background

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

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

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

8 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. Background

9 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) Methods

10 Neoadjuvant Chemotherapy Results 88 patients with 1 ◦ MPNST ( ) n=48 n=40 (45.4%) n=38

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

12 Results Characteristics p=0.032

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

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

15 Pathologic response rate correlates with disease free survival Results

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

17 Pathologic response rate correlates with disease specific survival Results

18 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 Conclusion

19 Acknowledgements Thank you!

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

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

22 MPNST Staging Background Advanced stage High gradeLarge Frequent metastasis AJCC staging Histopathologic grade Primary tumor size and depth Distant metastasis Regional lymph node metastasis Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp


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