1. 12 th Annual CTOS Meeting 2006 No of chordomas in NIRS Back ground: The number of chordomas treated with carbon ion radiotherapy have increased annually in NIRS. Purpose: To evaluate the clinical outcomes of carbon ion radiotherapy for sacral chordomas Patients and method: Patients eligibility; medically inoperable tumor or refusal of surgery Patients characteristics: Period; 06/ 96 – 03/ 04, No. of pts.; 41 (All pts. were followed over 2 years. ) Median age; 61 (51-84), Operation (+) / (-); 8 / 33 Median clinical target volume :502ml (135-1468) Method: Carbon ion radiotherapy with excellent dose distribution and biological effectiveness Applied dose; 52.8 - 73.6 GyE/16Fr. (70.4GyE; 32 pts.) Statistics: The follow-up period was calculated from the initial date of irradiation. 96% 50% 10% 0 5 10 15 20 25 22pts. 18 19 11 9 7 5 6 1 1 1 pts. 1996 2000 2003 2006 Oct primary post-ope

2. 12 th Annual CTOS Meeting 2006 Result: 2-year and 5-year local control rate; 98% and 94% Local recurrence (in field); 2 pts. at 13Mo and 35Mo 2-year and 5-year overall survival rate; 95% and 84% 3 pts.; died of disease, 4 pts.; intercurrent disease 2-year and 5-year disease free survival rate; 85% and 56% Metastases 12 / 41 pts. Function at the last follow-up date in 33 primary chordomas ambulatory; 32 pts.remaining, stoma; 2 pts.before referring to our hospital 2 pts.just after CIRT (ileus before CIRT) Urinary diversion; none Adverse reaction: 2pts. G4 late skin reaction Conclusion: We think carbon ion radiotherapy is the best treatment for chordomas, especially in elderly patients Before 3 years after Local control Overall survival (Mo)

3. 12 th Annual CTOS Meeting 2006

4. Comments Charged Particle Therapy Can Achieve High Rates of Local Control for Chordomas Rates of control may depend on whether RT is used for primary vs. recurrent disease MGH experience with high dose proton RT –(Park et al IJROBP 2006 65:1514) 87% local control for primary chordoma 14% local control for recurrent chordoma Late effects (sacral neuropathy) are unknown

5. 12 th Annual CTOS Meeting 2006 Background and Purpose Radiotherapy, in addition to surgery, is an important adjunct in the local management of adult soft tissue sarcomas (STS) but most types of STS do not appear to be particularly radiosensitive Myxoid liposarcoma, however, is comparatively radiosensitive and often shows reduction in volume when treated with preoperative radiotherapy. Thus use of radiotherapy might further improve local control in this disease We report the results of treatment of extremity myxoid liposarcomas in a multidisciplinary clinic. Methods Data was prospectively collected of patients treated at our centre between 1989 and 2004 1300 patients were treated for extremity soft tissue sarcoma (dermatofibrosarcoma protuberans excluded ). Limb-sparing surgery was performed, where possible Radiotherapy was used in patients with deep tumours where limb sparing would not have been achieved with wide margins residual tumour after ‘unplanned’ excisions positive microscopic margins. Pre- and post-operative radiotherapy dose (when given) was 50Gy and 60-66Gy, respectively. Adjuvant chemotherapy was not given routinely. Does radiosensitivity of myxoid liposarcoma translate into improved local control? Peter Chung, Anthony Griffin, Charles Catton, Peter Ferguson, Jay Wunder, Robert Bell, Brian O'Sullivan Radiation Oncology, Surgical Oncology and Musculoskeletal Oncology, Princess Margaret Hospital, Mount Sinai Hospital, University of Toronto, Canada Pre-radiotherapy Post-radiotherapy

6. 12 th Annual CTOS Meeting 2006 Results 110 patients - localized myxoid liposarcoma Median follow up 71 months Preoperative RT - 50 patients (45%), postoperative RT - 38 (35%), no RT - 22 (20%) 2 patients (2%) - primary amputation. Local recurrence - 2.7% (3/110), all positive margins. 2 – RT, 1 – no RT (contraindication) 5-year local recurrence-free survival - 97% (figure 1) 5-year disease-free and overall survival - 86% & 95% 12 patients developed metastatic disease 5 pulmonary 7 non-pulmonary 4-soft tissue, 2-bone, 1-lymph nodes 1190 patients - other sarcoma pathology Median follow up 45 months Preoperative RT - 501 patients (42%), postoperative RT - 317 (27%), no RT - 372 (31%) 63 patients (5%) - primary amputation Local recurrence developed - 9.5% (113/1190) 34 (30%) had positive margins 5-year local recurrence-free survival was 89% (figure 2) Conclusions Overall local control of extremity STS with multimodality management exceeds 90% Local control of myxoid liposarcoma compares favourably with that of other STS High rate of extra-pulmonary recurrence in myxoid liposarcoma seen Figure 1 Figure 2

7. 12 th Annual CTOS Meeting 2006 Comments Very high rates of local control are achieved with surgery + RT for myxoid liposarcoma Even for sarcomas not termed particularly “radiation sensitive” local control was greater than 90%

8. 12 th Annual CTOS Meeting 2006 Positive surgical margins in soft tissue sarcoma treated with preoperative radiation: Is a postoperative boost necessary? Ali H. AlYami, Anthony M. Griffin, Brian O’Sullivan, Peter C. Ferguson, Charles N. Catton, Peter W. Chung, Robert S. Bell, Jay S. Wunder Departments of Radiation Oncology and Surgical Oncology, Princess Margaret Hospital, Musculoskeletal Oncology Unit, Mount Sinai Hospital, The University of Toronto Purpose: Is use of postoperative radiotherapy (RT) boost following preop RT associated with a lower local recurrence rate in patients with positive surgical margins? Methods: Retrospective review 1986-2003; 1236 patients had surgery for STS (limb salvage, amputation) 233 had positive margins (18.8%); excluded those treated with chemo (n=17); 216 total RT deliveredN% None3817.6 Postop8539.3 Preop5224.1 Preop + postop boost 4119.0 Reason for no postop boost (total n=52) NLocal recurrence Re-excision intraop72 Re-excision (2 nd surgery)41 Wound complication111 Prior rads (dose limit)20 Amputation50 Planned positive100 Other (co-morbidity, low grade)132

9. 12 th Annual CTOS Meeting 2006 35 local recurrences overall (35/216, 16.2%) 6 in in the preoperative radiotherapy group (6/52, 11.5%) versus 9 in the preop/postoperative boost group (9/41, 22%) 4.5 yrs OR x 2 A postoperative RT boost following preoperative RT and positive margin surgery for STS did not show an advantage in preventing recurrence. Therefore the increased morbidity and cost associated with higher overall radiation doses may be avoided in this situation. Conclusions p= 0.13 p= 0.057 Margin classification as per Gerrand, JBJS Br 2001

10. 12 th Annual CTOS Meeting 2006 Pre-operative IMRT to 50 Gy /25 fractions Elekta Synergy Cone-beam CT unit Custom immobilization Boney anatomy match of CBCT and planning CT datasets On-line isocentre position verification and target volume assessment Isocentre deviations > 3 mm tolerance corrected by couch translations Notification of volume changes and replanning as necessary Random and systematic positioning errors used to compute PTV margin 3-D ISOCENTRE VERIFICATION AND VOLUMETRIC TARGET ASSESSMENT USING CONE-BEAM IMAGE GUIDANCE FOR LOWER EXTREMITY SOFT TISSUE SARCOMA Parent A. MRT(T), Euler C. MRT(T), White, E.MRT(T), Sie F. MRT(T), Sharpe M. PhD, Craig T. PhD, Griffin A. MSc,Ferguson P. MD, Chung P. MD,Catton C.MD, Wunder J.MD, O’Sullivan B. MD, FRCPC Departments of Radiation and Surgical Oncology, Princess Margaret Hospital, University Musculoskeletal Oncology Unit, Mount Sinai Hospital, University of Toronto Margin = 2.5  + 0.7   = Systematic errors  Random errors METHODS

11. 12 th Annual CTOS Meeting 2006 25 patients / 588 CBCT datasets RESULTS 25 Patients Fractions with isocentre shifts: 5 – 17, mean = 11 5 Pts with volume changes resimulated, 3 Pts replanned Positioning error determined a 7 mm uncorrected PTV margin Online corrections reduced margin to 3 mm VOLUME INCREASE VOLUME DECREASE POSITONING UNCERTAINTIES AND PTV MARGIN SOFT TISSUE VISUALIZATION CONCLUSIONS Daily CBCT verifies isocentre position and determines positioning deviations CBCT permits soft tissue visualization and assessment On-line correction of positioning uncertainties can reduce the PTV margin to 3mm CBCTPlanning CT Pathology Site

12. 12 th Annual CTOS Meeting 2006 Outcomes after Combined Modality Treatment of Retroperitoneal Sarcomas (#529) Ray, et al. University of Michigan Purpose: to review institutional experience, and identify RFs for LC, DM and OS Patients/Methods: 88 patients with retroperitoneal and deep truncal soft tissue sarcoma treated with combined modality therapy that included radiotherapy, retrospective analysis most patients high grade, LMS/Lipo, treated with postop RT

13. 12 th Annual CTOS Meeting 2006 Results: –2- and 5-year LC: 66% and 51%; DM: 38% and 51%; OS: 70% and 30% –Positive margins, larger tumor size, lower RT doses, male gender associated with increased local recurrence –High grade, incomplete surgical resection, male gender associated with worse survival –Patients with local failure had increased hazard of distant metastasis Conclusions: –Strategies to improve local control and reduce distant metastasis are needed: preop RT, more conformal RT, radiosensitizers, concurrent chemo/RT, adjuvant chemo

14. 12 th Annual CTOS Meeting 2006 Radiological “tissue responses” may add to dimensional responses to predict pathologic tumor response to preoperative chemo-radiation therapy in localized soft tissue sarcoma (STS). Stacchiotti S, Collini P, Messina A, Barisella M, Bertulli R, Grosso F, Dileo P, Piovesan C, Pilotti S, Olmi P, Lozza L, Gronchi A, Casali PG __________________________________ Objective. To correlate radiological and pathological patterns of tumor response to concurrent preoperative chemotherapy and radiation therapy in localized high-grade soft tissue sarcomas (STS). Methods. Between April 2002 and September 2006, 40 patients with localized high-risk STS of extremities or superficial trunk received 3 cycles of neoadjuvant Epirubicin + Ifosfamide and concomitant radiotherapy, followed by surgery, within a prospective Italian Sarcoma Group (ISG) trial. MRI were taken before the neoadjuvant treatment and before surgery. Radiologically, changes to tumor size and tissue characteristics, along with contrast enhancement variations, were recorded. Histologically, the percentage of residual tumor throughout the whole mass was tentatively scored according to the FNCLCC pretreatment grading system (0, 50), and the quality and quantity of post-treatment changes (necrosis, hemorrhage and sclerohyalinosis) were recorded. Results. According to RECIST, 14 patients (35%) had a PR while 2 patients had a PD confirmed histologically, in terms of more than 50% of residual vial tumor cells. 5 patients had a RECIST SD, without radiological changes suggestive of a “tissue response”: pathologically, there was more than 50% of residual tumour in all surgical specimens. Other 18 (45%) patients had a RECIST SD/PD, with radiographic signs of tissue changes: pathologically, the residual tumour was less than 50% in all (less than 30% in 11) but 4 carring a synovial sarcoma; 1 patient with a RECIST SD had radiological signs of tissue progression confirmed histologically with the presence of the 95% of vial tumor cells in the surgical specimen. Conclusions. Through RECIST criteria, we were able to appreciate only a proportion of pathologically responsive patients. Some kind of assessment of “tissue responses” on MRI may usefully integrate the dimensional data, in order to clinically predict the actual pathologic tumor response.

15. 12 th Annual CTOS Meeting 2006 # 40 Patients… Treatment… Epirubicin and Ifosfamide (EI) x 3 + radiation therapy surgery + EI x 2 Radiological “tissue responses” may add to dimensional responses to predict pathologic tumor response to preoperative chemo-radiation therapy in localized soft tissue sarcoma (STS). Stacchiotti S, Collini P, Messina A, Barisella M, Bertulli R, Grosso F, Dileo P, Piovesan C, Pilotti S, Olmi P, Lozza L, Gronchi A, Casali PG Histological types… # 11 pleomorphic sarcoma # 11 synovial sarcoma # 7 spindle cells sarcoma # 5 MPNST # 3 myxoid liposarcoma # 1 leiomyosarcoma # 1 myxofibrosarcoma # 1 pleomorphic rabdomyosarcoma high risk primitive localized soft tissue sarcoma of the extremities or trunk (high grade, diemension =/> 5 cm, deep site)

16. 12 th Annual CTOS Meeting 2006 RECIST criteria appreciated only a proportion of tumors that demonstrated a response pathologically.