mci breast symposium 2019 final...

4/9/2019

1

Marcio Fagundes, MDMedical Director – Radiation Oncology

Proton Therapy in Breast Cancer: Rationale, Applications and Challenges

MCI - Inaugural Women’s Cancer Symposium 4/5/2019Disclosures: none

Marcio Fagundes, MD MCI – Miami Cancer Institute

Pencil Beam Scanning Proton Therapy

High Dose Rate Brachytherapy

CyberKnife® M6™ GammaKnife® Icon™Varian® TrueBeam™

Viewray® MRIdian™Linac

Radixact

We can create proton backup plans for the best suited equipmentfor any given disease

Miami Cancer Institute = Comprehensive TechnologyA True Multimodality Approach (multiple platforms)

Prostate Brachytherapy

Accelerating Protons

In order for protons to be clinically useful for radiotherapy, they must be accelerated to high energy.

Radiotherapy is performed with protons of energy up to 250 MeV (mega-electron volts).

A 200 MeV proton travels at ~1/2 the speed of light.

Hydrogen atoms are separated into electrons and protons. Protons accelerated in a cyclotron.

Beam line

As acceleration increases so does energy and penetration in tissue

Particles extracted from cyclotron travel down a beam line to the treatment room

4/9/2019

2

Protons

Gantry CyclotronBeam line

Why Protons?

Dr. Herman Suit - Harvard / MGH Proton Center (1)

(1) Herman Suit, “The Grey Lecture 2001: Coming Technological Advances in Radiation Oncology,” International Journal of Radiation Oncology Biology Physics 53 No. 4 (2002): 798-809.

“Direct Radiation Complications Never Occur In Unirradiated Tissues”

“There is no advantage whatsoever to irradiating uninvolved healthy tissue”

Therapeutic ratio is increased by:

– More radiation in the tumor = increased disease control

– Less radiation in the healthy tissues = lower side-effect

Primary Goal of Radiation Therapy Technology Evolutionis aimed at Increasing Therapeutic Ratio

=Therapeutic RatioTumor Control

Normal Tissue Complications

Majority of advancements in the field have been based on this principle:

• IMRT, IGRT, respiratory gating, PET fusion• Deep inspiration breath hold technique• Prone breast treatment

Why Protons are Superior to Photons

ProtonsProtons are clinically superior to X-rays:

X – Rays do not stop

Excess radiation to healthy tissue results in costly side effects and secondary tumors

4/9/2019

3

The Value of Protons

Protons avoid unnecessary radiation

to heart, lungs, intestines delivered by X-rays

Protons avoid unnecessary radiation

to heart, lungs, intestines delivered by X-rays

Protons are physically superior to X-rays:

Protons

X-Rays do not stopContinue to travel into normal tissuesbeyond the target

Conventional Radiotherapy

Spare heartand coronaries

Use Protons

Unfavorableanatomy

Radiation therapy is an integral component of curative breast cancer treatment for many women

Majority of women with breast cancer are cured and will live long enough to suffer long term consequences of radiation

Increasing trend of treating regional nodes including IMN nodes

The breast and regional nodes lie in close proximity to the heart and lungs

Numerous publications have demonstrated that exposure to the heart and lungs can lead to serious morbidity and mortality

By reducing the exposure to the heart and lung, proton therapy may reduce radiation-related toxicity

Why protons for breast cancer ?

Sweden and Denmark: 2168 pts post-radiotherapy for Breast Cancer

Correlation between mean radiation dose to the heart and risk of major coronary events: Myocardial infarction

Coronary revascularizationDeath from ischemic heart disease

Risk of major coronary event increases by 7.4% per Gray of exposure to the heart1

1 Darby et al., “Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer,” New England Journal of Medicine 368(2013)

4/9/2019

4

Nilsson, et al. JCO 30(4) 380-386; 2012

Coronary Exposure to Radiation in Conventional Radiotherapy for Breast Cancer

Stenosis of the main coronary artery left anterior descending (LAD)

Exposure of the main coronary artery

Darby et al. NEJM 2013

- Cardiac morbidity increases by 7.4% with each extra Gy.

- Cardiac events also happen early in first 5 to 10 years of follow up

- There is no “safe” cardiac dose

Increased Heart Dose = Higher Cardiac Toxicity

HEART DOSE

Patients at higher risk for cardiac injury

• Patients not eligible for prone or DIBH treatment • IMN involvement (R or L sided)• Cardiotoxic chemo• Young age• Bilateral disease requiring bilateral XRT• Poor cardiac anatomy• Left medial tumors• Pre-existing cardiac disease• Prior thoracic radiation (lymphoma, breast cancer)

Ares et al., IJROBP 2009

For early stage breast cancer, “Prone Breast Photon XRT”: good option to lower

heart dose

Most patients treated to breast only are suitable for prone setupand will not require Protons

Left Breast Right Breast

4/9/2019

5

Evolving Radiotherapy Options when Lymph node treatment is required

Whole breast or chestwall + regional LN XRT

3D-Conformal XRT IMRT - Tomotherapy

Highest potential exposure of LAD

Can lower LAD dose but at the expense of extensive moderate dose levels to heart and lungs Intensity Modulated Radiotherapy (IMRT) with

Deep Inspiration Breath Hold (DIBH) can decrease heart exposure.

However, some patients do not tolerate breath hold techniques

Protons for whole breast radiation?Ares et al., IJROBP 2009

Protons for whole breast radiation?Ares et al., IJROBP 2009

Most benefit from protonsseen when comprehensivetarget includes:

chest wall or breast +

axilla, sclav and IMC nodes

4/9/2019

6

Older Proton Techniques: Double scatter or Uniform Scanning

Protons/SOBP

Compensate accounting for tissue inhomogeneity and distal shape of tumor

Lucite Compensator

Brass aperture shapes the beam

THE PAST: 2011-2012, Before PBS technique we used uniform scanning for breast treatment

Limited field size = requires multiple fields and match lines

Supraclavicular and axilla LN fieldField

edge

Match line

Chest wall and IMC LN field

Chest wall target

Sclav target

• Long treatment time + 45 min• Higher skin dose then PBS• Match lines subject to hot or

cold spots• ….


Miami Cancer Institute: Modern Proton Therapy

Pencil Beam Scanning

Deeper penetrating proton spots fill the deeper portion of the target first

Then shallower spots with lower energy (less penetrating) protons fill the remaining of the target volume.

single spot

Magnets steer protons

Target

ASTRO states that “in patients with breast cancer, it is recommended that the irradiated heart volume be minimized to the greatest possible degree without compromising the target dose” 1

Heart toxicity (cont)Abril 2015

Radiation type:

3-D CRT

VMAT

Tomotherapy

Minus the proton dose =

4/9/2019

7

3DCRT VMAT Tomo Protons

LAD mean dose 23.7 19.9 10.6 5.8 Gy

Heart mean dose 7.3 8.2 10.5 0.9 Gy

Total Lung V5 Gy 33.6% 54.6% 46.3% 20.6%

Contral. Breast mean 1.5 3.9 6.8 0.2 Gy

Unspecified normal tissue volume > 10 Gy(cc)

2817 3943 3504 353

ASTRO states that “in patients with breast cancer, it is recommended that the irradiated heart volume be minimized to the greatest possible degree without compromising the target dose” 1

1 Gagliardi et al., “Radiation dose-volume effects in the heart,” International Journal Radiation Oncology Biology Physics Supplement 2010: S77-S852 Fagundes, M. et al. “Cardiac Sparing Adjuvant Proton Radiotherapy for Stage IIII Breast Cancer Patients.” ASTRO 2013.

“Protons Maximizes Cardiac Sparing..” Fagundes et al. IJPT April, 2015

Consistent with ASTRO’s Statement:

Heart Dose Comparison between modalities

Marcio Fagundes, MD

IMPT - Chestwall with comprehensive LNSSIB IMC boost

50.4. Gy in 28 fxs of 1.8 Gy to CW, axilla, Sclav and entire IMC

56 Gy in 28 fxs of 2 Gy to upper IMC (+LN excised)

3 Field Composite Dose

Monoisocentric IMPT plan with gradient junction using 3 fields

AP

LAO RAO


4/9/2019

8

Gradient junction

IMPT plan and gradient junction

AP LAO RAO

Dose per field


IMPT: Coverage and Constraints

CTV

Heart

Total lungV20 = 8%

IMPTTarget coverage: D99 50.4 Gy

Mean heart dose: 0.06 Gy

LAD: D1 0.47 GyMean 0.09 Gy

Total lung: V20 8%V5 21%

Esophagus: D1 29.8 GyMean 4.2 Gy


Patient SetupImaging and Monitoring

C-RADPatient treatment setup and monitoring

Orthogonal X-raysSurface BBs for correlation

- C-RAD- KV/KV imaging with skin surface fiducials- CBCT


C-RADPatient treatment setup and monitoring

Note: the time shown in this figure is consistent with what we quoted in ASTRO abstract: The average treatment time per fraction, which included the pre-treatment imaging for setup, during treatment imaging

for verification and proton beam delivery of all fields, was 29:30 min (range from 17:26 to 69:06)

Monitoring during beam on

Treatment fraction completed in 21 minutes

Highly efficient pre-treatment imaging and delivery


4/9/2019

9

Tomotherapy Comparative plan

IMPT TomoTarget coverage: D99 50.4 Gy 50.4 Gy

Mean heart dose: 0.06 Gy 7.5 Gy

LAD: D1 0.47 Gy 26.7 GyMean 0.09 Gy 16.2 Gy

Total lung: V20 8% 26%V5 21% 87%

Esophagus: D1 29.8 Gy 33 GyMean 4.2 Gy 11 Gy

Tomotherapy

Patient completed proton treatment uneventfully without any downtime

Marcio Fagundes, MD MCI – Miami Cancer Institute MacDonald, S et al MGH - Harvard

Proton enables Bilateral Breast Treatment with minimal lung and heart exposure:

Yet another indication is patients who cannot raise the arm

Under such conditions, tangent photons or IMRT would result in significant exposure of the arm itself

IMPT – Intensity Modulated Proton Therapy Using split volume technique for Expanders

RAO field dose

Composite dose

+

LAO field dose

Good solution as long as the expander doesn’t rotate in the patient

Challenges: Large shift of metal port position of (5 cm) seen between simulation and treatment day can significantly impact dose distribution

Expander on the day of CT sim

Expander on Tx day of 2/22/2017Expander on Tx day of 2/16/2017

Expander on the day of CT sim

Saline Expanders (Metallic Port)Metal will have more stopping power on protons than

on X-rays radiation like IMRT

4/9/2019

10

MacDonald et al, RO 2013

Tangent Photons

Anatomy following bilateral implants are frequently not suitable for tangent photons or IMRT because of excessive exposure of:- Contralateral chest wall- Lung- Heart

15 Gy

5 Gy

IMRT

Mean heart dose 6-10 Gy

Protons

Mean heart dose < 1 Gy

Applications of protons post-mastectomy with implant Reconstruction: photons vs protons

(1) Herman Suit, “The Grey Lecture 2001: Coming Technological Advances in Radiation Oncology,” International Journal of Radiation Oncology Biology Physics 53 No. 4 (2002): 798-809.

Reducing radiation dose to normal tissue is not a research question (we already know it is toxic!)

We can only investigate the magnitude of the achievable gain by reducing normal tissue radiation dose.

Dr. Herman SuitHarvard / MGH Proton Center

Medical Vision

Locally Advanced Breast Cancer (Stage IIA‐IIIC) Requiring breast/chest wall and regional nodal RT

(including IMN)

RANDOMIZATION

Arm 2

Proton RT

Arm 1

Photon RT

Co-PIs: Shannon MacDonald (MGH) and Oren Cahlon (MSK)

45 - 50.4 Gy over 5-6 weeks daily treatments

Primary Objective

• To assess the effectiveness of proton vs. photon therapy in reducing major cardiovascular events (MCE)

• Primary hypothesis: For patients with locally advanced breast cancer, proton therapy will reduce the 10-year MCE rate after radiation from 6.3% to 3.8%

• Sample size: 1,716 patients -> 1200

4/9/2019

11

Participating Institutions

1 MGH-Massachusetts General Hospital (Boston, MA) 17. MCL- Karmanos / McLaren Proton Therapy (Flint, MI)

2. MDACC-University of Texas MD Anderson (Houston, TX) 18. TCPT – Texas Center for Proton Therapy (Dallas, TX)

3. UF-University of Florida (Jacksonville, FL) 19. UFO–Orlando Health (Orlando, FL)

4. OKC-Oklahoma City Procure (Oklahoma City, OK) 20. ACC–Ackerman Proton Center (Jacksonville, FL)

5. PENN-University of Pennsylvania (Philadelphia, PA) 21. OU–Oklahoma University (Oklahoma City, OK)

6. NWCH-Northwestern/Cadence Health (Chicago, IL) 22. HPTC–Hampton (Hampton, VA)

7. NJ-NY Proton/MSKCC Consortium (NYC & Somerset, NJ) 23. MAYO Clinic (Phoenix, AZ)

8. UW-University of Washington (Seattle, WA) 24. EU-Emory University (Atlanta, GA)

9. WUSTL-Washington University (St. Louis, MO) 25. WB-William Beaumont (Royal Oak, MI)

10. PROV-Provision (Knoxville, TN) 26. HOPK-Johns Hopkins (Washington D.C.)

11. UC San Diego (La Jolla, CA) 27. UTSW-UT Southwestern (Dallas, TX)

12. WK-Willis Knighton (Shreveport, LA) 28. GU-Georgetown University (Washington D.C.)

13. CINJ-Cancer Institute of New Jersey (New Brunswick, NJ) 29. CINN – University of Cincinnati (Cincinnati, OH)

14. MAYO Clinic (Rochester, MN) 30. MCI – Miami Cancer Institute (Miami, FL)

15. UM-University of Maryland (Baltimore, MD)

16. UH-Case-Western (Cleveland, OH)

• Proton therapy is most beneficial in breast cancer patients requiring comprehensive lymph node treatment including IMC

• …especially true for those who cannot tolerate DIBH IMRT

• Transient dermatitis during Tx can be enhanced with protons

• Magnitude of the long term benefit in cardiac toxicity reduction is being assessed by RadComp Trial

• Flap or permanent implant reconstruction is preferred if proton therapy is anticipated over saline expander

Conclusions

THANK YOU to our entire staff for the team work and high quality care we offer at MCI

Marcio Fagundes, MDMedical Director – Radiation Oncology

Miami Cancer CenterBaptist Health South Florida

[email protected]

mci breast symposium 2019 final...

Documents