1. The Influence of Age on Morbidity in Primary High Grade Sarcoma of the Extremity K. Alektiar, M. Brennan, S. Singer Memorial Sloan-Kettering Cancer Center

2. Introduction: STS & Age Wibmer C et al. Ann Oncol 2009

3. Local Recurrence & Age Cahlon O et al. ASTRO 2008

4. Use of RT and Older Age: MSKCC Data (n = 1459) Odds Ratio 95% CI p value Limb sparing surgery 13 7-25 < 0.001 High grade 3.6 2.4-4.7 < 0.001 Deep tumor 2.5 1.8-3.4 < 0.001 Size ≥ 5 cm 2.2 1.7-2.9 < 0.001 Positive margin 1.6 1.2-2.1 0.004 Age ≥ 70 0.6 0.5-0.9 0.005 Ashman et al. ASTRO 2006

5. Purpose To determine whether older age, defined as ≥ 70 years, influences morbidity in pts with primary HG extremity STS who received adjuvant RT at MSKCC

6. Patient Population  # of pts: 433  Period: 8/82- 02/06  Presentation: Primary, N0M0  Mean age: 53 (range: 16-89)  Grade: High only  Deep: 89% (n = 387)  Size > 5 cm: 74% (n = 322)  Lower extremity: 72% (n = 310)

7. Extent of Surgery All pts had limb-sparing surgery at MSKCC n % Bone manipulation ♠ 83 19 Nerve manipulation ♦ 115 27 Tissue transfer 31 7 ♠: Periosteal stripping/bone resection ♦: Neurolysis/nerve resection

8. RT Type All pts had their RT MSKCC n (%) Dose (Gy)* BRT 239 (55%) 45 EBRT 159 (37%) 63 BRT+EBRT 35 (8%) 20+45 Adjuvant chemotherapy: 139/433 (32%). *: Median dose

9. Sex Female Male 159 (47%) 180 (53%) 41(44%) 53 (56%) 0.5 Size (cm) ≤ 5 > 5 85 (25%) 254 (75%) 26 (28%) 68 (72%) 0.6 Depth Superficial Deep 33 (10%) 306 (90%) 13 (14%) 81 (86%) 0.25 Site Upper extremity Lower extremity 94 (28%) 245 (72%) 29 (31%) 65 (69%) 0.5 Adjuvant CT Yes No 127 (38%) 212 (62%) 12 (13%) 82 (87%) 0.001 < 70 ≥ 70 p Distribution of Variables

10. Extent of Surgery & Age Groups < 70 (n = 339)≥ 70 (n = 94)p Bone manipulation ♠ 63 (18%)20 (21%)0.5 Nerve manipulation ♦ 97 (29%)18 (19%)0.06 Tissue transfer 28 (8%)3 (3%)0.2 ♠: Periosteal stripping/bone resection ♦: Neurolysis/nerve resection

11. RT Type & Age Groups: For the purpose of this analysis, BRT and BRT+EBRT were combined < 70 (n = 339)≥ 70 (n = 94)p BRT/BRT+EBRT 220 (65%)54 (57%) EBRT 119 (35%)40 (43%) 0.18

12. RT “Conventional” Dose & Age Groups Conventional: BRT 45 Gy EBRT 60-70 Gy BRT+EBRT 15-20 and 45-50 Gy < 70 (n = 339)≥ 70 (n = 94)p BRT* 200 (91%)50 (93%)0.15 EBRT 108 (91%)35 (88%)0.2 *: BRT and BRT+EBRT

13. Morbidity Median F/U: 53 months n (%) Wound re-operation 33 8 Fracture 17 4 Stiffness 51 12 Edema 46 11 Nerve Damage ♠ 27 7 ♠:Those with nerve resection were excluded

14. Morbidity & Age < 70 ≥ 70 p Wound re-operation 7% 12% 0.09 Fracture 4% 3% 0.6 Stiffness 11% 15% 0.3 Edema 9% 18% 0.01 Nerve Damage ♠ 8% 4% 0.13 ♠:Those with nerve resection were excluded

15. Joint Stiffness n (%) Grade 0 382 88 Grade 1 26 6 Grade 2 20 5 Grade 3 5 1

16. Grade of Stiffness & Age Groups < 70 (n = 339)≥ 70 (n = 94) Grade 0 302 (89%)80 (85%) Grade 119 (6%)7 (7%) Grade 2 14 (4%)6 (6%) Grade 3 4 (1%)1 (1%)

17. Edema n (%) Grade 0 387 89 Grade 1 17 4 Grade 2 24 6 Grade 3 5 1

18. Grade of Edema & Age Groups < 70 (n = 339)≥ 70 (n = 94) Grade 0 308 (91%)79 (84%) Grade 113 (4%)4 (4%) Grade 2 15 (4%)9 (10%) Grade 3 3 (1%)2 (2%)

19. Grade of Nerve Damage: (n = 377/433) ♠ n (%) Grade 0 350 93 Grade 1 11 3 Grade 2 7 1.5 Grade 3 1 0.5 Grade 4 8 2 ♠:Those with nerve resection were excluded

20. Grade of Nerve ♠ Damage & Age Groups < 70 (n = 291)≥ 70 (n = 86) Grade 0 267 (92%)83 (97%) Grade 19 (3%)2 (2%) Grade 2 6 (1.5%)1 (1%) Grade 3 1 (0.5%)0 (0%) Grade 48 (3%)0 (0%) ♠:Those with nerve resection were excluded

21. Conclusion  Older age (≥ 70 years) is not associated with increased morbidity from treatment with the exception of edema  Strategies to minimize the risk of edema are warranted  Withholding adjuvant RT solely based on older age, for fear of potential morbidity doesn’t seem to be justified

23. Influence of Age on BRT Morbidity < 70 ≥ 70 p Wound re-operation 9% 11% 0.7 Fracture 2% 0.8 Stiffness 5% 6% 0.8 Edema 6% 11% 0.2 Nerve Damage ♠ 8% 2% 0.2 ♠:Those with nerve resection were excluded

24. Influence of Age on EBRT Morbidity < 70 ≥ 70 p Wound re-operation 3% 13% 0.03 Fracture 8% 5% 0.8 Stiffness 22% 28% 0.6 Edema 14% 28% 0.09 Nerve Damage ♠ 10% 6% 0.7 ♠:Those with nerve resection were excluded

25. Morbidity & Type of RT in < 70 BRT EBRT p Wound re-operation 9% 3% 0.05 Fracture 2% 8% 0.03 Stiffness 5% 22% 0.005 Edema 6% 14% 0.009 Nerve Damage ♠ 8% 10% 0.7 ♠:Those with nerve resection were excluded

26. Morbidity & Type of RT in ≥ 70 BRT EBRT p Wound re-operation 11% 13% 0.9 Fracture 2% 5% 0.7 Stiffness 6% 28% 0.006 Edema 11% 28% 0.07 Nerve Damage ♠ 1% 6% 0.7 ♠:Those with nerve resection were excluded

27. RT Type & Age Groups < 70 (n = 339)≥ 70 (n = 94)p BRT 188 (56%)51 (54%) EBRT 119 (35%)40 (43%)0.18 BRT + BRT 32 (9%)3 (3%)