1. Chiba Cancer Center, Chiba, Japan Shintaro Iwata Tsukasa Yonemoto Yoko Hagiwara Takeshi Ishii Division of Orthopedic Surgery Akinobu Araki Dai Ikebe Division of Surgical Pathology Hiroyuki Funatsu Division of Diagnostic Imaging, Chiba Cancer Center, Chiba, Japan CTOS 18 th Annual Meeting1 st Nov. 2013 Infiltrative Soft Tissue Sarcoma - Should We Excise Beyond Radiological Infiltration? -

2. Chiba Cancer Center, Chiba, Japan Infiltrative Growth of STS How should I resect?

3. Overall Survival Chiba Cancer Center, Chiba, Japan Infiltrative Growth on MRI Significantly Correlated with Poor Local Control Rate and Overall Survival for MFH Focal Infiltrative Focal Infiltrative Focal P=.014 P=.04 -Iwata et al. CTOS 2011 meeting Local Control Rate

4. Chiba Cancer Center, Chiba, Japan Adjuvant Radiotherapy was Not Beneficial for Patients with Infiltrative Growth and Positive Surgical Margins Focal Infiltrative -Iwata et al. CTOS 2011 meeting Infiltrative Focal RT(+) RT(-) RT(+) RT(-) P=.38 P=.08

5. Chiba Cancer Center, Chiba, Japan Does radiological infiltration pattern represent histological tumor infiltration?

6. Chiba Cancer Center, Chiba, Japan Q1: Do tumor cells actually exist in the radiographic infiltration? Clinical questions Aim of this study Q2: Should surgery be planed to include resecting the radiographic infiltration?

7. Chiba Cancer Center, Chiba, Japan Patients and Methods Inclusion criteria 1) Diagnosed with MFS, UPS, or LMS 2) Treated initailly at our institution between 2007 and 2011 Total: 41 patients Follow-up for survivals: 18 - 77 months (median 48 months)

8. Histological infiltration (H-inf ) - Distance from the tumor edge to the end of the atypical tumor cells Chiba Cancer Center, Chiba, Japan Patients and Methods Measurement of tumor infiltration Radiographic infiltration (R-inf ) - Length of high-intensity tail-like extension GdFS STIR R-inf H-inf

9. Chiba Cancer Center, Chiba, Japan Result 1 Correlation with H-inf and other factors FactornH-inf(+)H-inf(-)P Age (mean, years)7660.016 Location Superficial1174.25 Deep-seated301317 Size (mean, cm)87.83 Grade Grade 2231013.44 Grade 318108 Surgical margin Adequate311318.12 Inadequate1073 (+) (-) H-inf Age (years) (Fisher’s exact test, Mann-Whitney’s U-test) (P<.0001, Fisher’s exact test) H-inf (+)H-inf (-)Total R-inf (+)17219 R-inf (-)31922 Total202141

10. Chiba Cancer Center, Chiba, Japan Length (cm) R-inf STIR R-inf GdFS H-inf 0.8-5.3 0.4-6.7 0.1-6.0 Range (cm) Median2.42.01.5 P=.59 (Kruskal-Wallis test) Result 2 Relationship between H-inf and R-inf

11. Chiba Cancer Center, Chiba, Japan R-inf GdFS H-inf=0.81xR-inf+0.25 R 2 =.59 R-inf STIR H-inf=0.47x R-inf+0.25 R 2 =.28 H-inf (cm) (Pearson’s correlation coefficient) Result 2 Relationship between H-inf and R-inf

12. Chiba Cancer Center, Chiba, Japan Result 4 Prognostic factor analysis FactorOASPLCRP Site Extremity78.5785.28 Trunk89100 Location Superficial82.89100.16 Deep-seated8084 Size <8cm87.31100.042* ≧ 8cm 7577 FNCLCC Grade Grade 283.76100.033* Grade 37976 Surgical margin Wide85.19100.0017* Intra-infiltrate10056 Intra-tumor5067 H-inf Yes78.7976.047* No84100 (Log-rank test) Time (months) H-inf Probability Yes No P=.047 Time (months) Surgical margin Probability Wide Intra-tumor Intra-infiltrate P=.0017

13. Chiba Cancer Center, Chiba, Japan Discussion Q1: Do tumor cells actually exist in the radiographic infiltration? Actually tumor lesion, not edema! A1: YES, we should think so, at least on UPS and MFS. R-inf reflects H-inf. Sensitivity: 89% Specificity: 86%

14. Chiba Cancer Center, Chiba, Japan Discussion Q2: Should surgery be planed to include resecting the radiographic infiltration? If you ignore, tumor recur. A2: YES, we propose 2cm margin from the edge of the infiltration in GdFS MRI. H-inf R-inf (H-inf - R-inf) < 2cm - 13/14 (93%)

15. Chiba Cancer Center, Chiba, Japan Conclusion Radiographic infiltration of MFS and UPS as assessed by GdFS MRI correlated with histological infiltration. Wide resection with an “infiltration”- free margin would improve local control of these tumors.

16. Chiba Cancer Center, Chiba, Japan Thank you for your attention.