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
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