12 th Annual CTOS Meeting 2006 Back ground

: The number of chordomas treated with carbon ion 25

pts.

No of chordomas in NIRS primary post-ope

22pts.

19 18 radiotherapy have increased annually in NIRS. 20

Purpose:

15 11 To evaluate the clinical outcomes of carbon ion radiotherapy 10 for sacral chordomas 5

Patients and method:

1 0 Patients eligibility; medically inoperable tumor or refusal of surgery 1 1996 1 6 5 7 9 2000 2003

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.)

96% 50% 10%

2006 Oct

Statistics:

The follow-up period was calculated from the initial date of irradiation.

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.

1 Function at the last follow-up date in 33 primary chordomas 0.8

ambulatory; stoma; 32 pts.

2 pts.

2 pts.

Urinary diversion; none remaining, before referring to our hospital

Adverse reaction:

2pts. G4 late skin reaction 0.6

0.2

0

Conclusion:

0 20 Before 40 60 patients 3 years after Local control Overall survival 80 100 120

Carbon ion radiation therapy

3 Clinical Dose = 2.7 GyE 2.5

2 Clinical Dose (GyE) 1.5

1 Biological Dose (HSG) Physical Dose 0.5

RBE 2.38

RBE 3.0

RBE 1.63

RBE 2.0

1.13 Gy 0.9 Gy 12 th Annual CTOS Meeting 2006 1.84 GyE 0 0 50 100 Depth in Water (mm) 150 200

12 th Annual CTOS Meeting 2006

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

12 th Annual CTOS Meeting 2006 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

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.

Pre-radiotherapy Post-radiotherapy

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.

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

12 th Annual CTOS Meeting 2006

Table 1: Patient characteristics Grade 1 Grade 2 Grade 3 Deep Superficial Size < 5cm Size > 5cm Margin positive Margin negative Prior surgery myxoid liposarcoma n 17 80 13 85 25 26 84 19 91 42 15% 73% 12% 77% 23% 24% 76% 17% 83% 38% sarcoma other n 197 366 627 912 278 377 813 236 954 515 17% 31% 53% 77% 23% 32% 68% 20% 80% 43% 1.0

Figure 1 0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 24

Survival Function

48 72 96 120 144

LR free survival (months)

168 192 Survival Function Censored Figure 2

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%

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%); 216 total excluded those treated with chemo (n=17);

Reason for no postop boost N Local RT delivered N % (total n=52) recurrence None Postop 38 85 17.6

39.3

Re-excision intraop Re-excision (2 nd surgery) 7 4 2 1 Preop Preop + postop boost 52 41 24.1

19.0

Wound complication Prior rads (dose limit) 11 2 1 0 Amputation Planned positive Other (co-morbidity, low grade) 5 10 13 0 0 2

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%) Time to LR by margin classification Local recurrence- boost vs. no boost

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

0 p= 0.13

RADScode preop & boost preop only preop & boost censored preop only censored 24 144 168 48 72 96 120

Time to LR (months) Conclusions

•A postoperative RT boost following preoperative RT and positive margin surgery for STS did not show an advantage in preventing recurrence.

1.0

0.8

0.6

0.4

p= 0.057

0.2

4.5 yrs Margin classification Planned positive margin Positive after unplanned excision Surgical error Planned positive margin censored Positive after unplanned excision censored OR x 2 censored 0.0

0 50 100 150

Time to LR (months)

200 Margin classification as per Gerrand, JBJS Br 2001 •Therefore the increased morbidity and cost associated with higher overall radiation doses may be avoided in this situation.

12 th Annual CTOS Meeting 2006

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, C hung 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 METHODS

• • • • • • • • 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

Margin = 2.5

S

+ 0.7

s S

= Systematic errors

s =

Random errors

SOFT TISSUE VISUALIZATION Planning CT CBCT 12 th Annual CTOS Meeting 2006 Pathology Site 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

POSITONING UNCERTAINTIES AND PTV MARGIN VOLUME INCREASE VOLUME DECREASE 7 3 2 1 6 5 4 0 No Correction On-Line Correction AP 3.3

1.9

LR Random SI 4 2.3

3.4

2.4

AP 1.8

0.5

LR SI Systematic 1.6

0.5

1.4

0.5

AP 7 3 LR Margin SI 7 3 7 3 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

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

12 th Annual CTOS Meeting 2006

• •

Results:

– 2- and 5-year LC : 66% and 51%; OS : 70% and 30% DM: 38% and 51%; – 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

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, >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.

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 # 40 Patients…

high risk primitive localized soft tissue sarcoma of the extremities or trunk (high grade, diemension =/> 5 cm, deep site)

Treatment…

Epirubicin and Ifosfamide (EI) x 3 + radiation therapy surgery + EI x 2

Histological types… # 11 pleomorphic sarcoma # 11 synovial sarcoma # 7 spindle cells sarcoma # 5 MPNST # 3 myxoid liposarcoma # 1 leiomyosarcoma # 1 myxofibrosarcoma # 1 pleomorphic rabdomyosarcoma

12 th Annual CTOS Meeting 2006

RECIST criteria appreciated only a proportion of tumors that demonstrated a response pathologically.