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The Importance of Histologic Subtype for Outcome Prediction in Primary Retroperitoneal Sarcoma: A Single-Institution Study of 675 Patients Marcus Tan,

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Presentation on theme: "The Importance of Histologic Subtype for Outcome Prediction in Primary Retroperitoneal Sarcoma: A Single-Institution Study of 675 Patients Marcus Tan,"— Presentation transcript:

1 The Importance of Histologic Subtype for Outcome Prediction in Primary Retroperitoneal Sarcoma: A Single-Institution Study of 675 Patients Marcus Tan, Murray F Brennan, Deborah Kuk, Li-Xuan Qin, Narasimhan Agaram, Nicole Moraco, Aimée Crago, Samuel Singer Memorial Sloan-Kettering Cancer Center Sarcoma Disease Management Program

2 Retroperitoneal sarcomas (RPS) Complete resection is the only chance for cure Role of radiation therapy and chemotherapy remain controversial AJCC staging system of limited utility Increasing understanding of differences in histologic types and subtypes – Need for histology-based models to better predict patterns of failure for individual patients Histology & RP sarcoma

3 Aim and Hypothesis Aim: To determine the prognostic significance of histologic type/subtype in a large series of patients with primary retroperitoneal sarcoma Hypothesis: Each histologic type/subtype of retroperitoneal sarcoma is associated with distinct patterns of local and distant recurrence Histology & RP sarcoma

4 Methods Retrospective review of prospectively- maintained sarcoma database from July 1982 to July 2010 675 patients with primary, non-metastatic RPS (excluding desmoid & GIST) Median follow-up for survivors 4.3 years Survival calculated from time of initial operation Histology & RP sarcoma

5 Tumor Characteristics Variablen % Histologic subtype Liposarcoma: well-differentiated & myxoid186 28% Liposarcoma: dedifferentiated, round cell & pleomorphic213 32% Leiomyosarcoma: low grade18 2% Leiomyosarcoma: high grade132 20% Solitary fibrous tumor33 5% Malignant peripheral nerve sheath tumor23 3% Translocation-associated20 3% Not otherwise specified (NOS)35 5% Other14 2% Grade Low242 36% High431 64% Histology & RP sarcoma

6 Operative Details Variablen % Completeness of resection R0337 50% R1237 35% R258 9% Exploratory laparotomy only, no resection*43 6% Number of organs resected 0284 42% 1207 31% 2112 16% ≥372 11% Vascular resection performed67 10% Histology & RP sarcoma *Subsequently excluded from analyses

7 5 years 10 years DSD (n=632) 31%45% Histology & RP sarcoma n=632* p<0.0001 Disease-Specific Death (DSD) by histologic type/subtype (n=21) (n=32) (n=184) (n=227) (n=119) *Resected patients only

8 Multivariate analysis of DSD Variable HR95% CIp-value Histologic subtype (compared to well-differentiated LPS) Dedifferentiated, round cell & pleomorphic LPS, sarcoma NOS3.42.3-5.1<0.001 Low grade leiomyosarcoma1.20.3-4.90.78 High grade leiomyosarcoma3.92.5-6.3<0.001 Solitary fibrous tumor2.31.1-4.50.02 Malignant peripheral nerve sheath tumor4.32.0-9.2<0.001 Translocation-associated sarcoma3.82.0-7.3<0.001 Size 10-20cm vs <10cm1.20.8-1.80.44 ≥20cm vs <10cm1.51.0-2.30.07 Number of organs resected (≥3 vs <3)1.91.3-2.80.002 Completeness of resection (R2 vs R0/R1)2.51.6-3.8<0.001 Histology & RP sarcoma

9 Local Recurrence (LR) by histologic type/subtype 5 years 10 years LR (n=574) 39%45% n=574* p<0.0001 Histology & RP sarcoma *R0/R1 resections only (n=18) (n=29) (n=173) (n=197) (n=113)

10 Multivariate analysis of LR Factor HR95% CI P Histologic subtype (compared to well-differentiated LPS) Dedifferentiated, round cell & pleomorphic LPS, sarcoma NOS2.31.7-3.1<0.001 Low grade leiomyosarcoma 0.50.1-2.0 0.31 High grade leiomyosarcoma 0.80.5-1.5 0.55 Solitary fibrous tumor 0.10.02-0.8 0.03 Malignant peripheral nerve sheath tumor 1.10.4-2.6 0.92 Translocation-associated sarcoma 1.10.4-2.9 0.91 Completeness of resection (R1 vs R0) 1.51.1-1.9 0.01 Size 10-20cm vs <10cm 1.60.9-2.8 0.08 ≥20cm vs <10cm 2.11.2-3.8 0.01 Age (>60 vs ≤60 years) 0.60.5-0.8 p<0.01 Histology & RP sarcoma

11 Local Recurrence Nomogram DD LPS Low grade LMS High grade LMS WD LPS MPNST SFT Concordance index 0.69 Histology & RP sarcoma

12 Distant Recurrence (DR) by histologic type/subtype 5 years 10 years DR (n=632) 24%28% n=632* p<0.0001 Histology & RP sarcoma (n=21) (n=32) (n=184) (n=227) (n=119) *Resected patients only

13 Multivariate Analysis of DR Factor HR95% CI P Histologic subtype (compared to well-differentiated LPS) Dedifferentiated, round cell & pleomorphic LPS, sarcoma NOS4.72.4-9.0<0.001 Low grade leiomyosarcoma 5.31.5-19.3 0.01 High grade leiomyosarcoma 11.65.7-23.4 <0.001 Solitary fibrous tumor 6.32.6-15.3 <0.001 Malignant peripheral nerve sheath tumor 2.40.6-9.2 0.21 Translocation-associated sarcoma 6.52.7-16.0 <0.001 Number of Organs Resected 1 or 2 vs. 01.40.9-2.00.1 ≥3 vs. 0 2.41.4-4.4 0.002 Size 10-20cm vs <10cm1.81.1-2.80.01 ≥20cm vs <10cm1.20.7-2.00.51 Histology & RP sarcoma

14 Distant Recurrence Nomogram DD LPS Low grade LMS High grade LMSWD LPS MPNST SFT Other Concordance index 0.72 Histology & RP sarcoma

15 Natural History by Histologic Type/Subtype Histology & RP sarcoma Well-diff & myxoid liposarcoma Dedifferentiated, RC & pleomorphic liposarcoma High grade leiomyosarcoma Solitary fibrous tumor MPNST (n=21) (n=32) (n=184) (n=227) (n=119) Disease-Specific Death Local Recurrence Distant Recurrence

16 Natural History by Histologic Type/Subtype Histology & RP sarcoma Well-diff & myxoid liposarcoma Dedifferentiated, RC & pleomorphic liposarcoma High grade leiomyosarcoma Solitary fibrous tumor MPNST (n=21) (n=32) (n=184) (n=227) (n=119) Disease-Specific Death Local Recurrence Distant Recurrence

17 Natural History by Histologic Type/Subtype Histology & RP sarcoma Well-diff & myxoid liposarcoma Dedifferentiated, RC & pleomorphic liposarcoma High grade leiomyosarcoma Solitary fibrous tumor MPNST (n=21) (n=32) (n=184) (n=227) (n=119) Disease-Specific Death Local Recurrence Distant Recurrence

18 Natural History by Histologic Type/Subtype Histology & RP sarcoma Well-diff & myxoid liposarcoma Dedifferentiated, RC & pleomorphic liposarcoma High grade leiomyosarcoma Solitary fibrous tumor MPNST (n=21) (n=32) (n=184) (n=227) (n=119) Disease-Specific Death Local Recurrence Distant Recurrence

19 Natural History by Histologic Type/Subtype Histology & RP sarcoma Well-diff & myxoid liposarcoma Dedifferentiated, RC & pleomorphic liposarcoma High grade leiomyosarcoma Solitary fibrous tumor MPNST (n=21) (n=32) (n=184) (n=227) (n=119) Disease-Specific Death Local Recurrence Distant Recurrence

20 Summary Liposarcoma, leiomyosarcoma and SFT are associated with late recurrence and death from disease (as long as 15 years from initial diagnosis) Dedifferentiated liposarcoma and high grade leiomyosarcoma have similar DSS, but distinct patterns of local and distant recurrence. SFT is associated with low local recurrence (<10%) but high distant recurrence (40% at 5 years) Histologic type / subtype Completeness of resection Tumor size Number of organs resected Age DSD (R2 vs R0/R1) LR (R1 vs R0) DR Histology & RP sarcoma

21 Conclusions Histologic subtypes of RPS have distinct differences in the incidence and timing of local and distant recurrence, as well as disease specific death Multivariate models and nomograms estimating risk of DSD, LR and DR – Inform patients and physicians of an individual’s risk – May prove useful for selection of patients for clinical trials of: Neo-adjuvant radiation Neo-adjuvant/adjuvant chemotherapy Molecular targeted therapy Histology & RP sarcoma

22 Acknowledgements MSKCC Sarcoma Database July 1982-present n=10,150 patients 10,000 patients reached on May 21 st, 2013 Funding: NIH SPORE in Soft Tissue Sarcoma P50 CA 140146-01 NIH Soft Tissue Sarcoma program project grant P01 CA 047179 The David and Monica Gorin Sarcoma Fund

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