modern radiation therapy for breast cancer...modern radiation therapy for breast cancer: gary m....
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Improving results while reducing time and toxicity
Modern radiation therapy
for breast cancer:
Gary M. Freedman, M.D.
Professor
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This presentation is sponsored by Varian, and I am presenting on behalf of Varian
I am receiving an honorarium from Varian to make this presentation
Varian is paying travel expenses to allow me to make this presentation
Reflects my own opinions and not necessarily those of Varian or Penn Medicine
Conflicts of interest to report:
• None
Radiation treatment is not appropriate for all cancers. For product-specific safety information
and literature, please visit www.varian.com/safety.
Varian as a medical device manufacturer cannot and does not recommend specific
treatment approaches. Individual treatment results may vary.
Not all products or features available for sale in all markets.
LIST VARIAN EQUIPMENT/VERSION
Halcyon
Disclosures
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Objectives
Identify the recent major trends in radiation management of
patients with breast cancer that can improve outcomes and
reduce treatment times.
Use advanced technologies to optimize radiation target
coverage and reduce dose to the heart to minimize risks of
side effects.
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A Great Trend 1990 - Today
Breast cancer deaths have been decreasing since 1990
Siegel et al CA Cancer J Clin 2019;69:7-34.
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Lumpectomy + Radiation ~ 1990
Local-regional recurrence already < 10% by 1990
But treatment takes 6-7 weeks
High rates of grade 2-3 dermatitis, fibrosis
Wapnir et al J Clin Oncol 24:2028-37; 2006.
5 NSABP studies
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Making Lumpectomy + Radiation Better 1990 - 2020
Hattangadi-Gluth et al Int J Radiat Oncol Biol Phys 82: 1185-91; 2012.
No trastuzumab
Local control
• Recurrence reduced from <10% to <5%
– Refinements in patient selection (imaging, BRCA testing)
– Improved surgery, pathology, systemic therapy
– Radiation boost
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Making Lumpectomy + Radiation Better 1990 - 2020
Improved biology
• Hypofractionation based on concept of /
– Reduced length of treatment course from 6-7 to 3–4 weeks
– Equal local control
– Improved convenience and cost
TrialYears
Conducted
Patients
(Number)
Fractionation
(Gy/Fractions)
10-Year Local
Recurrence
OCOG 1993-1996 1,234
50/25
42.5/16
7%
6%
START A 1998-2002 2,236
50/25
41.6/13
39/13
7%
6%
8%
START B 1999-2001 2,215
50/25
40/15
5%
4%
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Making Lumpectomy + Radiation Better 1990 - 2020
Improved biology
• Hypofractionation based on concept of /
– Reduced length of treatment course from 6-7 to 3–4 weeks
– Reduced side effects
Michigan Radiation Oncology Quality Consortium
2309 evaluable patients (578 received HF).
Outcomes worse with CF vs. HF
• Moist desquamation, 28.5% vs 6.6%, P < .001
• Grade 2 dermatitis, 62.6% vs 27.4%, P < .001)
• Self-reported pain (moderate/severe pain, 41.1% vs 24.2%, P = .003)
• Burning/stinging bother (often/always, 38.7% vs 15.7%, P = .002).
• Hurting bother (33.5% vs 16.0%, P = .001)
• Swelling bother (29.6% vs 15.7%, P = .03)
• Fatigue (29.7% vs 18.9%, P = .02)
Jagsi et al JAMA Oncol 2015.
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Making Lumpectomy + Radiation Better 1990 - 2020
NCCN 2016
ASTRO Consensus 2018
Smith et al Pract Rad Oncol 8:145-52; 2018.
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Making Lumpectomy + Radiation Better 1990 - 2020
Improved physics – the largest gains in the past 30 years
• Improved target coverage
• Improved dose homogeneity
• Improved accuracy of delivery
• Reduced time for treatment
• Reduced toxicity of radiation
1990
C-Arm LinacToday
Halcyon
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1990
Fluoroscopic Simulation
Today
CT simulation
Then and Now
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Then and Now
1990
Fluoroscopic planning
Today
3D planning
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Then and Now
1990
2D plan
Today
3D planning
3D Dose to Volumes of the
Targets and Normal Organs
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Radiation Today
Whole Breast Radiation
Regional Node Radiation
Avoiding The Heart
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Contouring Targets
GTV_Boost
CTV_Boost
CTV_Breast
Contouring – based on RTOG and RADCOMP atlases
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3D Planning of Tangential Fields
Optimizing gantry angle, field size, collimator angle
Cover Targets
Stay to
midline
Avoid heart
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Isodose Plan
Plan Sum whole breast and boost
Boost
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Potential Halcyon Limitations - Energy
6 MV
Max 112.6%
Mixed 10 and 15 MV
Max 110.9%
Missing
PTV
coverage
PTV
covered
by 95%
isodose
Very large breast size (separation 29 cm)
need to be careful of coverage
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Dose Volume Histogram
PTVeval 95% volume ≥ 95% dose
Mean heart 176 cGy (goal is ≤ 300 – 400 cGy)
V20 Left lung 14% (goal is V20 ≤ 15-20%)
PTVeval_Breast
PTVeval_Boost
Lung
Heart
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Image Guided Radiation with Halcyon
Cone Beam CT
Pre-treatment verification of patient and beam alignment
Courtesy of Chris Kennedy, PhD
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Image Guided Radiation with Halcyon
Cone Beam CT
Pre-treatment verification of patient and beam alignment
Planning CT
Boost Target
Pre-Treatment CT
Verification of Alignment
Courtesy of Chris Kennedy, PhD
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Breast Treatment Efficiency with Halcyon
Treatment data for 30 patients on Halcyon
None Yaw Pitch Roll Other
96.7% 2.0% 0.4% 0.5% 0.5%
Reimaging frequency:
Treatment positioning quality:
Fair Acceptable Good Great
0.1% 5.4% 80.8% 12.7%
Courtesy of Chris Kennedy, PhD
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Radiation Today
Whole Breast Radiation
Regional Node Radiation
Avoiding The Heart
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Axillary Radiation
ACSOG Z0011
SNB +/- axillary dissection
Whole breast radiation – most had axillary coverage as well.
10 year survival, DFS, regional recurrence equal.
Giuliano et al JAMA 318:918-26; 2017.
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Axillary Radiation
Radiation coverage of the
axillary nodes in the
setting of SN + and
ACOSOG Z0011 type
patient
Coronal Lateral
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Regional Node Irradiation
EORTC AMAROS trial
Radiotherapy or surgery of the axilla after a positive SN
• 12% mastectomy
RT to all three levels of the axilla together with the medial part
of the supraclavicular fossa (50 Gy).
5-year axillary recurrence rate after a positive SNB was
• 0.4% (4/744) after ALND
• 1.2% (7/681) after ART
Donker et al 2014.
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Regional Node Irradiation
NCIC CTG MA.20
LR DFS 95.2% vs 92.2% (HR .59, p=.009)
Distant DFS 86.3% vs 82.4% (HR .76, p = .03)
OS 82.8% vs 81.8% (HR .91, p = .38)
Whelan et al NEJM 2015.
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Contouring Targets
Comprehensive nodal coverage
CTV_IMN
PTV_IMN
PTV_Axilla I-II
CTV_Axilla I-II
PTV_Axilla III
CTV_Axilla III
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Contouring Targets
PTV_Sclav
CTV_Sclav
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3D Planning Fields
Cover targets Block
shoulder
Block heart
Cover targets
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Radiation Today
Whole Breast Radiation
Regional Node Radiation
Avoiding The Heart
Nilsson et al J Clin Oncol 2012; 30:380-386.
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Postmastectomy Radiation Improves Survival But … Watch the Heart
Node Negative
Node Positive
Trials 1964 – 1986
Losing 3 - 4% - mostly
from late cardiac effects
EBCTCG
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Postlumpectomy Radiation Improves Survival But … Watch the Heart
Trials 1976 – 1999
Losing 1% - mostly from late cardiac effects
EBCTCG Lancet 378:771-84; 2011
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Avoiding the Heart - Prone
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Avoiding the Heart - Prone
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Potential Limitations – Halcyon Bore Size
Able to accommodate most very large patients
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Avoiding the Heart - DIBH
Deep Inspiration Breath Holding
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Avoiding the Heart - DIBH
Heart
Inside
Field
Outside
Field
Deep Inspiration Breath Holding
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Avoiding the Heart - DIBH
Large separation of heart from
targets as it moves inferior and
medial from chest wall.
Mean heart dose <250 cGy
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1990 2019
Early Stage Invasive Breast
Cancer
Lumpectomy
6-7 weeks Radiation
Now and Tomorrow
Early Stage Invasive Breast
Cancer
Lumpectomy
4 weeks radiation
1 week radiation
2029?
Early Stage Invasive Breast
Cancer
Lumpectomy
Oncotype Low
No Radiation
Oncotype High
4 weeks radiation
1 week radiation
Greater role for biology?
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Now and Tomorrow
2015 Medicare Access and CHIP Reauthorization Act (MACRA)
Reimbursement By Course (Not Fractions) = more hypofractionation
Hypofractionation requires excellent physics
• Homogeneity, accuracy, and heart avoidance
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A Great Trend 1990 - Tomorrow
Radiation – still an important role in multidisciplinary care
• Improves local-regional control
• Reduces breast cancer mortality
• May be alternative to larger surgery
• Modern treatment is faster, fewer days, less toxicity, less expensive
Thank you!
Gary M. Freedman, M.D.
Professor