1. Pulmonary Metastasis From Osteosarcoma Multi-factorial analysis of survival at first lung involvement Ali Aljubran, Martin Blackstein for the University of Toronto Musculoskeletal Oncology Group

2. INTRODUCTION  The cure rate of non-metastatic cases has improved from 20% (Pre chemotherapy era) to 65%.  Recurrence still occurs in approximately 30%.  More than 80% of all relapses involve the lungs.  Complete surgical resection is the only potential curative treatment.  Single institute review.

3. PATIENTS AND METHODS  Osteosarcoma patients (1988-2003).  Variables at the first lung involvement, e.g. RFI, multiplicity and laterality of lesions and size of the largest nodule are all analyzed. Peri operative chemotherapy was also analyzed.  Statistical methods: Post lung metastasis survival PLMS was calculated from the date of the first lung metastasis to the date of death or last follow-up.

4. RESULTS 247 Total 1988-2003 Synchronous Mets 38 (15.4%) M0 at presentation 209 (84.6%)

5. RESULTS 247 Total 1988-2003 Synchronous Mets 38 (15.4%) M0 at presentation 209 (84.6%) Metachronous Mets 56(26.8%) No relapse 145 (69.4%) Total 94 Isolated LR 8 (3.8%)

6. RESULTS Med. FU 2.7y 247 Total 1988-2003 Synchronous Mets 38 (15.4%) M0 at presentation 209 (84.6%) Metachronous Mets 56(26.8%) Isolated LR 8 (3.8%) No relapse 145 (69.4%) Isolated Bone 9 Lung Lung+/-others85 Total 94 DOD 58 (68.2%) AWED 12 (14.1%) ANED 15 (17.6%)

7. Characteristics 85 patients No. (%) Follow up (onset of lung mets) Median 2.7 year, (Range 0.1 y -16.25 y) Age at 1 st lung mets Median 29, (Range 14-77) Gender Male Female 53 (62.4) 32 (37.6) % Necrosis (Primary tumor) ≥ 90% <90% No pre-op chemo 26 (30.6) 48 (56.5) 11 (12.9) RFI before 1 st relapse ( 52 pts- metachronous lung met) ≤ 12 months >12 months Not applicable 28 (53.9) 23 (44.2) 1 (1.9) Lung surgery No surgery 1 surgery 2 surgeries 3 surgeries 4 surgeries Unknown 34 (40) 23 (27.1) 11 (12.9) 47 patients 10(11.8) (55.3) 3 (3.5) 4 (4.7)

8. Variables related to 1 st lung involvement ( only the operated cases, 47pts).. Number of lung metastases 1-3 ≥ 4 Unknown 18 (38.3) 25 (53.2) 4 (8.5) Laterality Bilateral Unilateral Unknown 32 (68.1) 12 (25.5) 3 (6.4) Size of the largest nodule >1 cm ≤ 1cm Unknown 20 (42.5) 13 (27.7) 14 (29.8) Peri-op chemotherapy Status of resection Yes No Unknown Complete Incomplete Unknown 21 (44.7) 25 (53.2) 1 (2.1) 35 (74.5) 5 (10.6) 7 (14.9)

9. 85 patients: 3 year PLMS: 30%

10. 3 year PLMS: Synchronous mets: 30 % Metachronous mets: 30 %

11. 3 year PLMS: NO lung surgery: 16 % lung surgery: 38 %

12. 3 year PLMS: 1-3 lesions: 69 % ≥ 4 lesions: 18 %

13. 3 year PLMS: Unilateral: 55 % Bilateral: 32 %

14. 3 year PLMS: ≤ 1 cm: 67 % > 1 cm: 34 %

15. 3 year PLMS: No chemo: 39 % Chemo: 33 %

16. DISCUSSION LATEST LARGE SERIES StudyNo. of patients Conclusions/ Prognostic factors COSS Group; JCO, Jan 2005 436 257: >18y 422 operated Median FU is 1.2 year. 3 year PRS is 29 %. Long time to relapse, unilaterality and no pleural involvement are important prognostic factors. Ferrari et al; JCO, Feb 2003 136 Age®: 5-47y 114 operated 3 year PRS is 33 %. RFI, size and number of lesions. No support for adjuvant chemo after complete metastectomy. Meyer et al; Cancer, Jan 1987 59 39 operated Sex and number of nodules have impact on survival. Belli et al; Cancer, Jun 1989 44 20 operated 5 year OS is 37%. Post metastectomy chemotherapy probably prevent new lung lesion. Carter et al; Thorax, Oct 1991 43 25 operated 5 year PRS is 20%. Location of lesions ( one lobe or different lobes). DFI, No. and laterality of lesions not important.

17. CONCLUSION  This is a large series from single center that primarily includes adult patients with median follow up of 2.7 years.  The 3 year PLMS is 30% which is comparable to previous large studies.  Surgical resection doubled the survival at 3 years.  Both Synchronous and Metachronous lung metastasis have similar survival.  Lung nodules of <4, size ≤ 1cm and unilaterality are favorable prognostic factors.  The use of chemotherapy with the resection did not appear to affect the survival.

18. ACKNOWLEDGMENT Anthony Griffin Melania Pintilie

19. THANK YOU