1. Chondrosarcoma of the Pelvis Prognostic Factors and Survival Analysis at 10-20 Years Matthew J. Seidel, MD Patrick P. Lin, MD Valerae O. Lewis, MD Christopher P.Cannon, MD Alan W. Yasko, MD

2. Literature Author/Yr#PtsFollow-up10-Yr SurvPelvic only? Comment Pring 20016412 yr med 97% (gr1), 75%(gr2), 14%(DD) Y Few High-Grade (1-gr 3, 7-DD) Berg 20016913 yr mean67%N Not all resected; sacrum, spine included Mochizuki 2000 1353.9 yr mean65%N Short f/u, data by stage, sacrum included Ozaki 1997315.5 yr med45%Y Short f/u, small #pts, data by stage Sheth 1996679.6 yr med--Y Recurrent tumors included

3. Goal of Study Define long-term oncologic outcome and prognostic factors for chondrosarcoma arising in the pelvic bones

4. Study Design Pelvic chondrosarcoma Surgically treated with curative intent Minimum 5 year f/u for living patients –5 year potential f/u for deceased patients Exclusion: –Sacral epicenter –Recurrent presentation –Metastatic presentation –Prior resection/surgery (other than biopsy)

5. Data Collection Retrospective medical record review including operative, pathology, and radiology reports –Demographics –Tumor grade, size, location, physical characteristics –Surgical type and margins –Timing and location of local recurrence and metastasis Long-term data from clinical follow-up, phone call, or letter

6. Statistics Kaplan-Meier survival –Disease-specific survival –Local recurrence-free survival –Distant relapse-free survival Log rank (determine difference between KM curves) Chi-square or Fisher’s exact test

7. 101 Patients Collection period: 1948- 2000 Follow-up: 5 to 45 years –Overall median 6 year follow-up –Living patients: median 13 year follow-up 31 female, 70 male

8. Overall Survival Status At Last Follow-up –41 NED – 1 AWD –45 DOD –13 DOC – 1 DUC

9. Grade 34 Low 24 Intermediate 27 High 16 Dedifferentiated

10. Epicenter Ilium: 57 Pubis: 24 Acetabulum: 10 Ischium: 10

11. Tumor Characteristics Mean Size: 18.5 cm –Range 3 to 25 cm Extra-osseous extension in 91 (90%)

12. Surgical Surgery Type –Amputation: 37 –Limb salvage: 64 Surgical Margins –Negative: 56 –Positive: 42 –Not Specified: 3

13. Disease-Specific Survival 5-Year10-year20-Year Low88%85%72% Intermediate70%45% High42%39%35%

14. Disease-Specific Survival 5-Year10-year20-Year Low88%85%72% Intermediate70%45% High50%45%38% DD 31% (15 mo) 31% ---

15. DSS: Prognostic Variables VariablePrognosticP-value Dedifferentiated Y <.0001 High Grade Y.0001 Cross Midline Y.0004 Displace Bladder Y.001 Local Recurrence Y.007 Intermediate Grade Marginal.07 Size >=10 cm Marginal.08 Amputation (vs. LSS) Marginal.08 Extra-osseous extension N.11 Positive Margin N.13 Epicenter N.45

16. Effect of LR On DSS Significant decrease in survival for patients with LR P=.007

17. Effect of LR On DSS Low Grade Significant survival difference P=.003

18. Effect of LR On DSS Intermediate Grade Marginal significance P=.08

19. Effect of LR On DSS High Grade Not Significant P=0.42

20. Results – Local Recurrence 35 Local Recurrences –Mean time 29 months –Range 3 to 120 months 91% (32/35) occurred within five years 3 Local Recurrence after five years –84 months (low-grade) –108 months (intermediate-grade) –120 months (low-grade)

21. Results – Local Recurrence 68% of LR (23/34) associated with positive resection margins Negative Margin (56) Positive Margin (42) LR10 (17.9%) 23 (54.8%) P=.002 No LR46 (82.1%)19 (45.2%)

22. Local Recurrence-Free Survival 5-Year10-year20-Year Low73%66% Intermediate49%37% High63%

23. LR – Prognostic Variables VariablePrognosticP-Value Positive MarginY.0002 Cross MidlineY.007 Displace BladderY.001 Size >= 10cmMarginal.06 Pubis EpicenterMarginal.06 Non-Pubis EpicenterN.12 High-GradeN.19 Extra-osseous extensionN.25 DedifferentiatedN.35 Surgery (Amp vs LSS)N.91

24. Results - Metastasis 28 Metastasis –Mean time 22 months –Range 1-114 months Location –Lung most common (27) –Other locations: liver (4), brain (2), spine (2), kidney (1), heart (1), pericardium (1), humerus (1), lymph node (1), scalp (1)

25. Results - Metastasis 93% (26/28) metastasis occurred in first four years Two metastasis occurred after four years –74 months (low-grade; LR at 23, 36, 41 months) –114 months (intermediate-grade; LR at 108 months)

26. Results - Metastasis 26/28 (93%) DOD at last follow-up –Median time 9 months 2/28 (7%) –DOC (1): NED 5 years after wedge resection at 24 mo –AWD(1): alive 4 years, wedge resection pending Metastasis has a significant negative effect on DSS (p<.0001)

27. Distant Relapse-Free Survival 5-Year10-year20-Year Low91%88% Intermediate76%61% High51%46%

28. DR-Prognostic Variables VariablePrognostic (Y/N)P-Value AmputationY.0004 DedifferentiatedY.002 High-GradeY.002 Displaced BladderY.02 Size >= 10 cmMarginal.08 Local RecurrenceN.19 Positive MarginN.30 Extra-osseous extensionN.43 Cross MidlineN.55 LocationN.68

29. Study Limitations Diminishing number of patients at 20 years –39% >10 yr f/u –17% >20 yr f/u Changes in mode and quality of radiographic imaging over study period Vagaries of histological grading Limited long-term radiographic imaging

30. Conclusions Long term follow-up data show LR or metastasis can occur beyond five years No first LR or metastasis was seen after 10 years

31. Conclusions Local Recurrence has a significant negative effect on long term survival –Most pronounced for low and intermediate grade tumors. Metastasis overwhelmingly resulted in death

32. Conclusions Significant prognostic factors at late follow- up are unchanged from short-term follow- up data –Disease-specific survival –Local recurrence-free survival –Distant relapse-free survival

33. Conclusions Evidence-based post-operative surveillance strategy should include at least 10 year follow-up after initial resection