POG – 8651 neoadjuvant chemo vs. immediate surgery and adjuvant chemo

1. Effects of Neoadjuvant Chemotherapy on Image-directed Planning of Surgical Resection for Distal Femur Osteosarcoma Kevin B. Jones, Brian Lam, Anthony M. Griffin, Yair Gortzak, Kevan Saidi, Michael C. Biddulph, Majid Al-Yamani, Lawrence White, Benjamin Deheshi, Sevan Hopyan, Peter C. Ferguson, Jay S. Wunder

2. POG – 8651neoadjuvant chemo vs. immediate surgery and adjuvant chemo • Intended 4 year accrual for 215 patients • Only 20 patients enrolled in first year • Down-sized to non-inferiority model with110 patients • After 7 years accrual, only 106 patients, 6 exlcuded • NO SIGNIFICANT DIFFERENCES 69±8% survival for immediate surgery 61±6% survival for neoadjuvant

3. Effects of Neoadjuvant Chemotherapy on Local Disease • Volume reduction? • Clearing of peritumoral edema? • Creation of a reactive rind/capsule?

4. Questions • Can surgeons consistently evaluate an MRI and plan a surgical resection? • Will that planned resection change from pre-chemotherapy to post-chemotherapy MRIs?

5. Methods • 24 patients with distal femur osteosarcoma • Pre- and post-chemo MRIs, blinded • 4 faculty sarcoma surgeons • Surgical planning assessment form

6. Surgical Planning Record • What type of surgical resection: • Hip disarticulation; amputation; borderline limb salvage; safe limb salvage • Expected myectomies: • % of each regional muscle • Expected neurovascular margins: • Millimeter distance from each structure • Expected soft-tissue coverage: • Anticipated need for flaps and grafts • Guess at MRI timing: • pre- or post-chemo

7. Other Assessments • Each surgeon repeated surgical planning for 5 blinded scans • 4 sarcoma surgery fellows evaluated scans from 5 patients • Each MRI was also evaluated by two experienced musculoskeletal radiologists

8. Statistics • Intra-class correlation coefficients for intra-rater and inter-rater reliability • Student’s t-test for continuous variables pre- to post-chemo • Fisher’s Exact test for categorical variables pre- to post-chemo

9. Results: Intra-rater reliability • Mean ICCs showed strong reliability • Surgeon 1: 0.794 (95%CI 0.692-0.865) • Surgeon 2: 0.597 (95%CI 0.429-0.725) • Surgeon 3: 0.889 (95%CI 0.829-0.928) • Surgeon 4: 0.832 (95%CI 0.745-0.884)

10. Results: Inter-rater reliability • Among faculty surgeons: ICC = 0.772 (95%CI 0.736-0.886) • Among faculty + fellow surgeons: ICC = 0.605 (95%CI 0.540-0.671)

11. Conclusions #1 • Surgeons can reliably record an intended surgical resection from an MRI • The details of that surgical resection are more determined by characteristics of the tumor anatomy than of surgeon preferences

12. Results: Pre- to Post-chemo • Many tumors changed in each direction • Net changes across the group were not statistically significant • Most trends were toward bigger, more risky surgeries after chemotherapy

13. Hip Disarticulation AKA Borderline Limb-salvage Safe Limb-salvage Pre-chemotherapy MRI Post-chemotherapy MRI

14. Of Note • Only 4 were poor responders (50% or less necrosis) histologically • 4 were fair responders (51-90% necrosis)

15. Conclusions #2 • In terms of the anatomic parameters of surgical resection, osteosarcomas as a group are not favorably affected by neoadjuvant chemotherapy

16. Thanks!