1. IMRT, Designed with Evidence-Based Bone Avoidance Objectives, Reduces the risk of Bone Fracture in the management of Extremity Soft Tissue Sarcoma Colleen Dickie MSc, MRT(T)(MR) Assistant Professor, University of Toronto UHN Princess Margaret Cancer Center

2. Acknowledgements Anthony M. Griffin, MSc Amy Parent, MRT(T), BSc, CMD Michael B. Sharpe, PhD Peter C. Ferguson, MD, FRCSC Jay S. Wunder, MD, FRCSC Peter Chung, MD, FRCPC Charles N. Catton, MD, FRCPC Brian O’Sullivan, MD, FRCPC Princess Margaret Cancer Center

3. Background Holt et al. Fractures following RT and Limb-Salvage Surgery for LE-STS: JBJS 2005 Sternheim et al. Internal fixation …high rate of failure: Bone Joint J 2013;95-B:1144–8. Severe morbidity  Review of 22 pts with internal fixation for fracture  Complications in 86% (82% non union at 12 mos)  13 pts underwent 24 revision operations 364 LE-STS EBRT  Females, > 55 yrs, thigh tumor location  Periosteal stripping  High (60-66 Gy – 10 %) vs. Low (50 Gy -2%)  Overall – 6.3 % crude risk  Median F/U = 58 mos

4. Background 1989 - 2004 Lack of 3D info 21 pts 24 fractures: 53 control  Matched on gender, tumour size / location, age, beam arrangement, RT timing / RT dose Fracture Risk reduced if:  V40 kept below 64%  Mean bone dose < 37 Gy  Max bone dose < 59 Gy Dickie et al. Bone Fractures following EBRT… IJROBP 2009 Nov 15;75(4):1119-24.

5. Objective To evaluate the potential for IMRT to reduce the risk of bone fractures:  Lower extremity soft tissue sarcoma (LE-STS)  Combined modality local treatment Evidence based Bone Avoidance Objectives (BAO)  V40 kept below 64%  Mean bone dose < 37 Gy  Max bone dose < 59 Gy Dickie et al. Bone Fractures following EBRT… IJROBP 2009 Nov 15;75(4):1119-24.

6. Methods / Materials Study timeframe: 2005 – 2011 230 plans employed BAO from our previous study  176 lower extremity  54 upper extremity Study confined to weight bearing bones to minimize reporting bias  i.e. Removed upper extremity cases (176 LE-STS) All patients: Surgery combined with RT  155 received preop (50 Gy)  21 received postop (60 – 66 Gy)  2 Gy per fraction daily

7. Methods / Materials 4 patients re-irradiated for in field recurrent disease  44 Gy / 40 fractions BID 6 hours apart 5 patients re-irradiated for recurrent disease at edge  50 Gy in 25 fractions We evaluated:  Mean bone dose  Max bone dose  Volume of Bone receiving > 40 Gy (V40)  Mean dose to the clinical target volume (CTV dose)

8. Results Target Coverage Criteria 100 % BAO achieved: 96 % preop, 72 % postop RT plans 4 patients experienced a bone fracture (2.2 %)  All preop 50 Gy / 25 f, 1 further 44 Gy / 40 f  3 males, 1 female Mean F/U= 47 mos

9. 9 First Fracture Case 46 yr old Male - Crane operator Myxoid Liposarcoma Rt Calf Preop RT & Sx 2007 15 mos post Tx spiral fracture Trauma by metal crane ring within RT volume > 58 Gy coincided with fracture site Treated conservatively 2008 2011 High dose >58Gy 2007 CTV mean = 50.9 Gy Bone mean = 30.6 Gy Bone max = 58.7 Gy Bone V40 = 37 % PASSED

10. 10 Second Fracture Case Original Retreat 10 cm UPS RT Thigh 55 yr Male Preop RT 2008 Sx 2009 In- field recurrence 2010 Retreatment Second RT course: IMRT 44 Gy / 40

11. 11 Second Fracture Case Proximal femur fracture 2012- fall at home 41 mos post Tx IM nail / Iliac crest bone graft 6 mos no healing Cemented proximal femur tumor prosthesis 2013 2012 2013 1 st Plan CTV = 51.7 Gy Bone mean = 35.5 Gy Bone max = 49.8 Gy Bone V40 = 31 % BID plan CTV = 40 Gy Bone mean = 15 Gy Bone max = 35 Gy Bone V40 = 1 %

12. Third Fracture Case 63 yr old Male Fibrosarcoma RT Thigh Preop RT & Sx 2007 Disease > 60% circumferential Fall - Fracture May 2008 IM nail inserted GTV High RT dose FAILED CTV mean 52.7 Gy Bone mean 41.4 Gy Bone max 52.9 Gy Bone V40 75.9 %

13. 13 Fourth Fracture Case UPS RT thigh 57 yr Female Preop RT Disease > 60% Circumferential 19 mos post Tx- pain Undisplaced transverse fracture IM nail GTV CTV mean = 51.9 Gy Bone mean = 26.1 Gy Bone max = 53.7 Gy Bone V40 = 39 % PASSED

14. Conclusions Risk of fracture using BAOs is lower than previously reported  (2.2 % vs. 6.3 %) Preferential use of preoperative RT  adverse RT morbidities  RT volumes and doses Bone objectives are practical and beneficial Bone sparing techniques should be employed for:  Circumferential disease  In re-irradiation settings  For women > 55 yrs

15. Acknowledgements Anthony M. Griffin, MSc Amy Parent, BSc, MRT(T) Michael B. Sharpe, PhD Peter C. Ferguson, MD, FRCSC Jay S. Wunder, MD, FRCSC Robert S. Bell, MD, FRCSC Peter Chung, MD, FRCPC Charles N. Catton, MD, FRCPC Brian O’Sullivan, MD, FRCPC Princess Margaret Cancer Center