1. Operative Management of Osteosarcoma Patients with Pulmonary Metastasis Jen Kramer, MD R2 Swedish Medical Center February 2011

2. Case Report 2008, 16 yr F Rt knee pain: Biopsy: osteosarcoma Metastatic workup negative. Multimodal tx: chemotx + resection

3. Chemotherapy: Cisplatin, doxorubicin, methotrexate, neulasta Feb 2010: resected and reconstructed w knee replacement May 2010: local recurrence. AKA. Metastatic workup negative until Jan 2011.

4. 1/25/2011

6. My Questions: 1.Palliative or curative? 2.Options for surgical approach? 3.Risks and benefits of staged versus simultaneous thoracotomies? 4.Exploratory contralateral thoracotomy for unilateral metastasis?

7. Introduction to OS Arise from primitive mesenchymal cells –osteoblastic (50%) –chondroblastic (25%) –fibroblastic (25%) Incidence: 8-11 million/year at 15-19 yrs of age Most common primary solid malignancy of the bone in children.

8. Introduction to OS Associated with Li Fraumeni syndrome (p53), retinoblastoma (RBI), Rothman-Thompson syndrome Treatment algorithm: –Pre operative chemotherapy –Resection –Adjuvant chemotherapy

9. Introduction to OS Presentation: pain, swelling, fracture 20% present with metastasis, most commonly the lung The most important predictor of survival in patients with osteosarcoma pulmonary metastasis is surgical resection.

10. Literature 1.Su WT, Chewning J, Abramson S, et al: Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases. J Pediatr Surg 39(3): 418-23, 2004 2.Zarroug A, Hamner C, et al: Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric population. J Pediatr Surg 41(4):647-51, 2006 3.Karplus G, McCarville M, et al: Should contralateral exploratory thoracotomy be advocated for children with osteosarcoma and early unilateral pulmonary metastases? J Pediatr Surg 44(4) 665-71, 2009

11. Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases. Retrospective review 43 patients 1980-2002 Memorial Sloan- Kettering Cancer Center New York. All 43 pts w unilateral mets on CT had ipsilateral thoracotomies. –15 negative explorations. –28 had metastasis confirmed at initial thoracotomy: 14 had extensive pleural or extrapleural disease. 14 are separated in to early versus late mets (2 yr cutoff). 4

12. Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases. 14 are separated in to early versus late mets (2 yr cutoff). –9 Early: 7 had contralateral disease (78%) –5 Late: 1 had contralateral relapse (20%). Recommend bilateral exploration in patients presenting with unilateral pulmonary nodules within 2 years of diagnosis due to high rate of bilateral metastasis in this population (78%). 4

13. Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric population Retrospective review 30 patients 18 years or younger from 1994-2004 at the Mayo Clinic Rochester. 21 sarcoma, 4 Wilms, 3 indeterminate pulmonary nodules, 2 germ cell tumors 5

14. Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric population Total 22 bilateral staged and 13 bilateral simultaneous thoracotomies. Endpoints: operative times, mean hospital stay, ICU stay, days with tube thoracostomy and time to initiation of adjuvant chemotherapy. 5

15. Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric population All endpoints demonstrated benefit for patients with bilateral simultaneous thoracotomies versus staged thoracotomy. Bilateral thoracotomy does not appear to increase post op morbidity or mortality over staged and may have certain benefits. 5

16. Should contralateral exploratory thoracotomy be advocated for children with osteosarcoma and early unilateral pulmonary metastases? Retrospective review 109 pts 1980-2005 with early pulmonary metastasis (with in 2 yrs of diagnosis) at St. Jude Children's Memphis. 81 pts with bilateral metastasis on preop imaging and 28 with unilateral mets on pre-op imaging. Main endpoint was side of recurrence for unilateral metastasis. 2

17. Should contralateral exploratory thoracotomy be advocated for children with osteosarcoma and early unilateral pulmonary metastases? 28 unilateral mets. –16% had recurrence in the ispsilateral –23% had recurrence in the contralateral lung No statistically significant difference between the incidence of recurrence in the ipsilateral and contralateral lung (P=0.18). Concluded that there was similar incidence of recurrence in the ipsilateral and contralateral lung. 2

18. Conclusion More questions: –Does contralateral exploratory thoracotomy improve survival? –Does improved CT sensitivity improvement null benefits of contralateral operative exploration?

19. References 1.Castagnetti M, Delarue A, et al: Optimizing the surgical management of lung nodules in children with osteosarcoma Thoracoscopy for biopsies, thoracotomy for resections. Surg Endosc 18(11): 1668-71, 2004 2.Karplus G, McCarville M, et al: Should contralateral exploratory thoracotomy be advocated for children with osteosarcoma and early unilateral pulmonary metastases? J Pediatr Surg 44(4) 665-71, 2009 3.Kaste S, Pratt C, et al: Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis Imaging features. Cancer 86(8): 1602-1608, 1999 4.Su WT, Chewning J, Abramson S, et al: Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases. J Pediatr Surg 39(3): 418-23, 2004 5.Zarroug A, Hamner C, et al: Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric population. J Pediatr Surg 41(4):647-51, 2006