Modern radiation therapy for breast cancer...Modern radiation therapy for breast cancer: Gary M....

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