1. Pt ZJ 19yo M that presented to Seattle Children’s for evaluation of 3 lesions found on recent PET CT ◦ One large mass in the posterior mediastinum just above the diaphragm ◦ A second near the superior vena cava ◦ A third anteriorly in the right chest just near the insertion of the diaphragm Scheduled procedure: Right Thoracotomy

2. CT 08/01/11

3. CT 08/01/2011

4. Pt ZJ Originally presented as a 14 year old with complaints of pain in his left leg just proximal to his knee Found to have a 14 x 6 cm mass in his left femur Additionally, found to have a 17-mm nodule in the left lower lobe He underwent biopsy of his left leg in March 2007, which revealed chondroplastic osteosarcoma

5. Pt ZJ He was subsequently started on cisplatin, doxorubicin and methotrexate December 2007 he underwent resection of left lower leg tumor, but not pulmonary nodule Resection demonstrated 55% necrosis with negative surgical margins Ifosfamide and etoposide were added d/t poor tumor response 1 st pulmonary recurrence (left lung) in June ’10, which resulted in a left thoracotomy 2 nd pulmonary recurrence (right lung) in March ’11, which resulted in a left thoracotomy 3 rd pulmonary recurrence (right lung) in June ‘11

6. Pulmonary Metastasis & Osteosarcoma Dale Wilson, MS4 University of Washington School of Medicine

7. Question(s) What is the prognosis of patients with osteosarcoma who develop pulmonary metastasis? What is the role of surgery?

8. Outline Epidemiology Pathophysiology Prognosis Role of surgery

9. Epidemiology age 0-24 Represents <1% of all cancers diagnosed Most common primary bone tumor affecting children and young adults Male > Female Race: others > blacks > whites Females have earlier first peak incidence Increased incidence for males between 1974-2004

10. Pathophysiology Mesenchymal origin Cancerous cells produce increased bone matrix Large percentage have acquired genetic abnormalities Mutations of RB and p53 gene Loss of heterozygosity of 3q, 13q, 17p and 18q Hematogenous spread

11. Prognosis 5-year survival of non-metastatic diasease reported to be between 60-70% With pulmonary metastasis this drops to 20- 40% Prognostic indicators for survival ◦ Chemonecrosis ◦ Pulmonary metastasis at time of diagnosis ◦ Number of nodules ◦ Bilateral vs. unilateral ◦ Central vs. peripheral

12. A retrospective review of patients 0-21 years old with a diagnosis of Osteosarcoma with pulmonary metastasis on CT between ‘85 and ‘00 115 patients with osteosarcoma with pulmonary metastasis, of which 84 had resection and 55 of those had CT scans to review 47 patients were described as having either central or peripheral lesions P. A. Letourneau., J. Pediatric Surgery (2011) 46, 1333–1337

13. Surgery Benefit Surgery provides a clear survival benefit which is supported by the literature Required for cure

14. M. T. Harting et al., J Pediatric Surgery 41 (2006), pp. 194–199 A retrospective cohort study of patients 0-21 with Osteosarcoma and pulmonary metastasis between ‘80-’00. 137 patients were included of which, 99 underwent surgical resection of pulmonary metastasis and 38 did not. Patients that underwent resection had a mean survival of 33.6 months. Those that did not had a mean survival of 10.1months and only 1 survivor at 5 years. Disease free interval and primary tumor necrosis were strong predictors of survival. measures of tumor burden were less prognostic

15. Repeated Surgery The survival benefit remains in the setting of repeat resection for metastatic disease. ◦ C. Fengshi et al., Repeat resection of pulmonary metastasis is beneficial for patients with osteosarcoma of the extremities., Interactive Cardiovascular and Thoracic Surgery., 2009; 9: 649-653 - 25 total pt with pulmonary metastasis; 23 underwent complete resection; 14 underwent repeat resection; the OS was 42.9% at 2yrs and 19% at 5yrs. ◦ S. Bielack et al., Second and Subsequent Recurrences of Osteosarcoma: Presentation, Treatment, and Outcomes of 249 Consecutive Cooperative Osteosarcoma Study Group Patients., Journal of Clinical Oncology., 2009; 27: 557-565 - 5 year OS for the second recurrence was 16% however, went up to 32% when a renewed surgical remission was achieved.

16. References L. Mirabello, R Troisi, S. Savage., Osteosarcoma Incidence and Survival Rates From 1973- 2004. Cancer. 2009;115:1531-43 R. Gorlick, P. Anderson, I. Andrulis., Biology of Childhood Osteogenic Sarcoma and Potential Targets for Therapeutic Development: Meeting Summary. Clinical Cancer Research., 2003;9:5442-5453 D. D. Rasalkar et al., Pulmonary metastases in children with osteosarcoma: characteristics and impact on patient survival., Pediatric Radiology., 2011;41:227-236 M.T. Harting et al., Long-term survival after aggressive resection of pulmonary metastasis among children and adolescents with osteosarcoma., Journal of Pediatric Surgery., 2006; 41:194-199 P. A. Letourneau et al., Location of pulmonary metastasis in pediatric osteosarcoma is predictive of outcome., Journal of Pediatric Surgery., 2011; 46: 1333-1337 C. Fengshi et al., Repeat resection of pulmonary metastasis is beneficial for patients with osteosarcoma of the extremities., Interactive Cardiovascular and Thoracic Surgery., 2009; 9: 649-653 S. Bielack et al., Second and Subsequent Recurrences of Osteosarcoma: Presentation, Treatment, and Outcomes of 249 Consecutive Cooperative Osteosarcoma Study Group Patients., Journal of Clinical Oncology., 2009; 27: 557-565 Up to Date A. Rosenberg., Pathologic Basis of Disease, eighth edition., Chapter 26, pages 1225-1226