CTOS 2013Radiation Oncology Session Discussion

Elizabeth H Baldini, MD, MPH

Associate Professor of Radiation Oncology

Harvard Medical School

Brigham and Women's Hospital and

Dana-Farber Cancer Institute

I have no disclosures.

“Making the Case for IMRT”

3D Conventional vs IMRT

3D (Conventional)Fixed beams deliver

uniform dose

Conform dose to the target

Dose gradient less steep set-up less crucial

Less expensive

IMRTBeams deliver variable

dose intensity

Sculpts dose to better conform to target

Dose gradient is steep set-up must be precise

More expensive

3D vs IMRT Dose Distributions*

IsodosesRed: 100%; Light blue: 20-30%*Hong, IJROBP 59:752; 2004

IMRT and Local Control

Late Effects of Pre-operative Image-Guided Radiation Therapy (IGRT) in

Extremity Sarcoma Patients: Results of RTOG 0630

Wang D, Zhang Q, Eisenberg B, Kane J, Li A, Lucas D, Freeman C,

Trotti A, Hitchcock Y, Kirsch D

RTOG multi-center trial

RTOG 0630

• 79 Patients with extremity STS

• Treated with pre-op RT + S

• RT Technique: 75% IMRT

• 3-year LR: 7 %

Quantitative Dosimetric Analysis of Patterns of Local Relapse After IMRT

for Primary Extremity Soft Tissue Sarcomas

Lanning R, Berry S, Folkert M, Alektiar K

Memorial Sloan-Kettering Cancer Center, NY

MSKCC

• 165 Patients extremity STS

• Treated with S + RT–79% post-op RT

• RT technique: 100% IMRT

• 5-year LR: 8.4%

Local Control Rates for Modern Series3D Conventional and IMRT: Similarly Excellent

5-yr LRRT Modality3D vs IMRT

RT Sequence

Patient Number

NCIC RCT, 2004O’Sullivan

6%, 7% 100% 3D Pre-op + Post-op

190

BWH/DFCI, 2013Baldini

10% 84% 3D Pre-op 103

MSKCC, 2013Alektiar

14.3% 100% 3D 88% Post-op

155

MGH, 2010Kim

11.5% 88% 3D Pre-op 56

PMH, 2013O’Sullivan

11.8% 100% IMRT (flap sparing)

Pre-op 59

MSKCC, 2013Lanning

8.4% 100% IMRT 79% Post-op

165

RTOG 0630, 2013Kirsch

7%(3-yr)

75% IMRT Pre-op 79

IMRT and Late Effects

Subcutaneous Fibrosis, Joint Stiffness, Edema

Bone Fracture

Wound Complications

Subcutaneous Fibrosis, Joint Stiffness, Edema

Late Effects of Pre-operative Image-Guided Radiation Therapy (IGRT) in

Extremity Sarcoma Patients: Results of RTOG 0630

Wang D, Zhang Q, Eisenberg B, Kane J, Li A, Lucas D, Freeman C,

Trotti A, Hitchcock Y, Kirsch D

RTOG Multi-Center Trial

RTOG 0630 vs NCI Canada Randomized Trial*Late Toxicity at 2 Years

RTOG 0630 Pre-op Arm NCIC

> Grade 2 Toxicity 10.5% 37%

Subcutaneous Fibrosis

5.4%** 31.5%

Joint Stiffness 5.4%** 17.8%

Edema 5.2%** 15.1%

*O’Sullivan, Lancet 2002, 359:2235; Davis, Radiother Oncol 2005, 75:48**Wang, IJROBP 2013, 87:S63

•Authors compare their results to NCIC trial

RTOG 0630 vs NCI Canada Randomized Trial*Study Details: Some Major Differences

RTOG 0630 Pre-op Arm NCIC

Study Era 2008-10 1994-97

Evaluable Patients 57 73

Follow-up Median 27 mos Minimum 21 mos

Clinical Target Volume

Smaller(2-3 cm margin on GTV)

Larger(4 cm margin on GTV)

RT Technique 75% IMRT 100% 3D

Late effect assessment schedule & tools

Same Same

*O’Sullivan, Lancet 2002, 359:2235; Davis, Radiother Oncol 2005, 75:48

Other Late Toxicity Results Modern Era with IMRT

Institution PMH* MSKCC** RTOG 0630*** Pre-op Arm NCIC

Study Era 2005-09 2002-10 2008-10 1994-1997

Patient Number 51 165 57 73

Treatment Modality

100% IMRT (sparing flap)

100% IMRT (79% post-op)

75% IMRT 100% 3D

Subcutaneous Fibrosis

9.3% NS 5.4% 31.5%

Joint Stiffness 5.6% 14.5% 5.4% 17.8%

Edema 11.1% 7.9% 5.2% 15.1%

*O’Sullivan Cancer 2013, 119:1878; **Alektiar IJROBP 2013, 87:S63 2008,26:344-0 and personal communication***Wang, IJROBP 2013, 87:S63

•Use of IMRT may be the main reason for reduced toxicity

Bone Fracture

Evaluation of Femur Fracture Risk in Soft Tissue Sarcoma of the

Thigh Treated with IMRT

Folkert M, Singer S, Brennan M, Boland P, Alektiar K

Memorial Sloan-Kettering Cancer Center, NY

MSKCC Results

• 82 patients treated with S + RT

• RT technique: 100% IMRT

• Fracture Rate 6.1%

• Expected Fracture Rate using PMH Nomogram: 26.4%

• This finding is not surprising …

PMH Nomogram Derived from 3D Era

• Patients treated 1986-2006

• RT Technique: 100% 3D RT

• Examined variables we might now consider proxies for more accurate variables

– Sex– Age – Compartment– Tumor Size– Radiation Dose– Periosteal Stripping

A Modern Era Comparison

• Subsequent PMH report from 2009*

• Examined dosimetric parameters

Lower risk of bone fracture if:»V40 < 64%»Mean bone dose < 37 Gy»Max bone dose < 59 Gy

• Agree with MSKCC authors that clinical variables in nomogram are less predictive

• Dosimetric variables are more predictive

*Dickie, IJROBP 75:1119; 2009

IMRT, Designed with Evidence-Based Bone Avoidance Objectives, Reduces

the Risk of Bone Fracture in the Management of Extremity Soft Tissue

Sarcoma

Dickie C, Sharpe M, Chung P, Griffin A, Parent A, Catton C, Ferguson P,

Wunder J, O’Sullivan B

Princess Margaret Hospital, Toronto

PMH Results

• 230 patients treated with IMRT

• Employed bone avoidance objectives: » V40 < 64%» Mean bone dose < 37 Gy» Max bone dose < 59 Gy

• Fracture rate: 1.7%

• Lower than prior report of 6.3% (3D)

• Demonstrates – Validity of bone avoidance objectives– Objectives largely achievable with IMRT– Fracture rate much lower than prior rates in 3D series

Wound Complications

In Depth Analysis of Wound Complications Following Preoperative Radiotherapy for Lower Extremity Soft

Tissue Sarcoma Patients

Dickie C, Griffin A, Moseley J, Biau D, Parent A, Sharpe M, Chung P, Catton C, Ferguson P, Wunder J,

O’Sullivan B

Princess Margaret Hospital, Toronto

PMH Methods

• 59 Patients

• Treated with IMRT to spare the surgical flap

• PTV coverage prioritized over flap-sparing

PMH Results

• Wound Complications (WC):– 30.5% (flap-sparing IMRT)– 43% from NCIC trial (3D)

• WC were further reduced when 92% of flap spared– 14.3% when <1% overlap of flap and PTV*

• Flap-sparing and ability to reduce WC can ONLY be achieved using IMRT

*O’Sullivan Cancer 2013, 119:1878

Conclusions

• IMRT Excellent Local Control –As good as, if not better than 3D– (Lanning, Kirsch, O’Sullivan)

• IMRT Less Late Toxicity vs 3D–Subcutaneous Fibrosis, Joint Stiffness,

Edema (Kirsch, Alektiar, O’Sullivan)

–Bone Fracture (Folkert, Dickie)

–Wound Complications (Dickie)

Conclusions

Abstracts presented today combined with other published literature:

“Make the Case for IMRT”

Clinical Implications

IMRT Should be Standard of Care

for Most Cases of Extremity STS

Dana-Farber / Brigham and Women’s Cancer Center:Center for Sarcoma and Bone Oncology

• Surgical Oncology Monica Bertagnolli, MDChandrajit Raut, MD, MSc

• Medical OncologyJames Butrynski, MDDavid D’Adamo, MDGeorge Demetri, MDSuzanne George, MDJeffrey Morgan, MDAndrew Wagner, MD, PhD

• PathologyChristopher Fletcher, MDJonathan Fletcher, MDJason Hornick, MD, PhDAlessandra Nascimento, MD

• Radiation OncologyElizabeth Baldini, MD, MPHPhilip Devlin, MDKaren Marcus, MD

• Orthopedic OncologyMarco Ferrone, MDJohn Ready, MD

ebaldini@partners.orgebaldini@partners.org