Proton Therapy & Why It Matters To You - MemberClicks · • The current gold-standard for...

Proton Therapy & Why It Matters To You

Samuel Marcrom, MD

Allison Paige Dalton, BS, CMD, R.T.(T)

Disclosures• Employer: University of Alabama at Birmingham

• Paige Dalton is Past President of the Medical Dosimetry Certification Board

• Paige Dalton currently serves as the AAMD liaison from the MDCB.

• Sam Marcrom currently serves on the Executive Committee for the Association of Residents in Radiation Oncology

Why does this matter to you?

1. At some point, a patient will likely ask you about it.

2. At some point, you will probably wonder about it.

3. As we are all working together to help treat patients with cancer, it is good to have an idea about who could benefit from the treatment.

4. It is good to know that proton therapy doesn’t solve every problem, and it does introduce some new challenges.

Photon Technology Improvements

Early X-ray Tube Orthovoltage Cobalt-60 Unit

More Skin Dose Less Skin Dose

Higher EnergyLower Energy

Photon Technology Improvements

Early LINAC Modern LINAC

Less Skin Dose

Higher Energy

More Skin Dose

Lower Energy

Image Credits: Notes on Physics for Residents in Radiation Oncology. 2002. Kenneth Ekstrandhttps://www.researchgate.net/figure/The-schematic-diagram-of-a-linear-accelerator_fig2_297806150

Problem 1: Skin Dose

To get enough dose here…

…it gets really hot here.

Higher beam energy improves the ratio of dose at depth vs. surface some, but not enough

Image Credits: Notes on Physics for Residents in Radiation Oncology. 2002. Kenneth Ekstrand

Isodose lines decrease because of (1) inverse square law and (2) attenuation by tissue

* **

Opposed beams

Significantly improves ratio of dose at depth vs. at surface

Image Credits: Notes on Physics for Residents in Radiation Oncology. 2002. Kenneth Ekstrand

Image Credits: https://radiologykey.com and https://sites.duke.edu/

Cartoon Analogy of Photons (X-rays)

= Photons (X-rays)

= Tumor

LINAC

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

Review of Conventional (X-ray) RTD

ose

Depth

Tumor

Review of Conventional (X-ray) RTD

ose

Depth

Tumor

Review of Conventional (X-ray) RTD

ose

Depth

Tumor

Volumetric Modulated Arc Therapy (VMAT)

Challenges with Photon Irradiation

• Relatively shallow maximum dose distribution (~2-4cm)• Creates a challenge in treating deep-seated tumors

• Dose deposition beyond the target (significant exit dose)

• Lateral penumbra = radiation scatters to the side

• These factors collectively result in irradiation of non-tumor normal tissue, which limits the chance of curative treatments without significant toxicity risks, particularly in tumors that are close to radiation sensitive normal tissue.

Extra Dose: The Physics of It

Efstathiou, J. A., Gray, P. J., & Zietman, A. L. (2013). Proton beam therapy and localised prostate cancer: current status and controversies. Br J Cancer, 108(6), 1225-1230. doi:10.1038/bjc.2013.100

Extra Dose: The Biology of It

Frank, S. J., Blanchard, P., Lee, J. J., Sturgis, E. M., Kies, M. S., Machtay, M., . . . Foote, R. L. (2018). Comparing Intensity-Modulated Proton Therapy With Intensity-Modulated Photon Therapy for Oropharyngeal Cancer: The Journey From Clinical Trial Concept to Activation. Semin Radiat Oncol, 28(2), 108-113.

doi:10.1016/j.semradonc.2017.12.002

Are there any benefits to protons other than informing the way you should think?

Protons on the scene, opened in 1990 at Loma Linda University Medical Center

Cartoon Analogy of Photons (X-rays)

= Photons (X-rays)

= Tumor

LINAC

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

Cartoon Analogy of Protons

= Protons

= Tumor

Cyclotron

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

Fear with Protons

= Protons

= Tumor

Cyclotron

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

Advantages of Proton Therapy

• Bragg Peak (decreased exit dose or dose beyond target)

• Increased, Fixed RBE (accepted to be 1.1 – but some debate about it being slightly higher at distal edge of Bragg Peak) • For every Gray given, the impact on killing the cancer is ~10%

more

• Ability to use fewer beam angles, further sparing normal tissue

Take Home #2: For a single proton beam still has entrance dose, but exit dose is minimal.

Image Credits: www.floridaproton.org

Decreased Exit Dose

Evidence of the distal edge of the proton beamProves high quality of entire treatment workflow

T1-weighted MRITreatment plan dose distribution

6 monthafter

Proton RT

Fatty changesin irradiated part of vertebral bodies

Cranio-Spinal Irradiation @ HIT

Passive Scattering Active Scanning

• Passive Scattering was developed first

• Active Scanning is a newer technique with some advantages

Proton Technology is Improving too! vs.

• RM (Range Modulator) – change the pristine peak range (creates SOBP)

• SS (Second Scatterer) – creates a flat beam

• RS (Range Shifter) – change the beam energy to the desired range in the patient

• AP (Aperture) – patient specific brass aperture to block protons lateral to target

• RC (Range Compensator) – custom plastic block cut to achieve distal conformity

DeLaney and Kooy. Proton and Charged Particle Radiotherapy. 2008

Range Modulator Aperture & Range Compensator

Passive Scattering

Scatterers

Tumor

Aperture

Rangemodulator

Dose Delivered

Compensator

Pencil Beam Scanning

• Facilitates complex dose distributions

• Tumors are radiated slice by slice

• All areas of a tumor treated with a specific energy are administered in the configuration -> The next energy level is employed until the entire tumor is treated

Magnetic Steering of Ion Beams (Scanning)

• As photons lack a charge, they are unable to be magnetically steered

• Protons and Carbon Ions can be magnetically steered

• This allows for highly customizable dose administration to conformally irradiate a non-uniform tumor shape.

Pencil Beam (Spot) Scanning

TumorSteering Magnets

Passive Scattering:

Pencil Beam

TumorSteering Magnets

Pencil Beam (Spot) ScanningPassive Scattering:

Pencil Beam

TumorSteering Magnets

Pencil Beam (Spot) ScanningPassive Scattering:

Pencil Beam

Pencil Beam (Spot) ScanningPassive Scattering:

TumorSteering Magnets

Dose Delivered

Pencil Beam

Pencil Beam Scanning

Types Of Proton Beam DeliveryPassive Scattering:

Pencil Beam Scanning:

• Passive scattering:

• Conformal only at the distal end of the beam

• Uses “open fields” for treatment

• Patient-specific apertures and compensators are manufactured for each beam

• The main type of proton therapy until very recently

• Pencil beam scanning:

• Conformal at the proximal and distal beam end

• Patient-specific devices not required

• Possibility for interplay effect

• The current gold-standard for proton therapy, with use increasing only in last few years

Comparison of RT Techniques

IMRT Proton Passive Scattering Proton Pencil Beam Scanning

Grosshans et al, Neuro Oncology, 2017

Rapid Rise in Particle Therapy Centers Wordwide

Courtesy of Particle Therapy Co-Operative Group

• 92 centers in operation • 31 in US

• 45 centers under construction • 9 in the US

*Data as of March 2019

The Proton Center at UAB

From the Ground Up

Construction at UAB

Professor Proton gives a tour

Cool Facts

Questions / Discussion

Proton Therapy: We are Learning and So Can You

Are Protons For Everyone?

Photo courtesy of Proton International

Challenges & Cautions with Proton Therapy

• Uncertainties and Disagreement regarding clinical benefit

• Range Uncertainty = Is it going where I think it is?

• Robustness = Will I still hit the cancer if things change? (swelling, weight loss, etc.)

• Expense and Facility Requirements

What is all this about range and being robust?

Range? Robust?

Fear with Protons

= Protons

= Tumor

Cyclotron

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

TumorSteering Magnets

Pencil Beam Scanning (PBS)a.k.a. Spot Scanning

Pencil Beam

Beam AnglesHead and Neck Prostate Breast/Chestwall

Although less beams can be used for treatment, angles must be chosen more carefully, paying attention to:• areas of inhomogeneities• structures/cavities within body that may change shape/fill during treatment• where beam ends (range uncertainty and RBE uncertainty)

Robustness needed for Range Uncertainties

Modified from Placidi et al, IJROBP, 2017

Planning CT On Treatment CT

Poor target coverage

Proton dose deposition much more sensitive to

tissue changes in the beam path

Re-Simulation during treatment

• Need for re-CT and re-planning is much higher when treating with Protons

• Estimated 25-40% of cases re-planned at some point during treatment

Head and Neck Site

Frequency of CT evaluation while on treatment

Definitive Oropharynx, Larynx and Thyroid

Weeks 2, 3 and 4

Nasopharynx, Nasal Cavity, Paranasal Sinus and Other Sinuses

Once weekly

Patel, Samir M.D; Anand, Aman Ph.D.; Bues, Martin Ph.D. 2016 Mayo Clinic Cancer Center

Moving Targets with Passive Scatter

• Monitor target motion to create ITV

• Irradiate ITV simultaneously

• Target is covered independent of position

Robustness Needed for Moving Targets

Spot delivery to a moving volume introduces the need for planning and delivery modification.

The limitations of proton therapy can result in toxicity / side effects.

• Utilization and planning need to be needs to be stepwise, methodical, and thoughtful.

• Low-Grade Glioma on biopsy with questionable areas of enhancement

• Treated with Protons

• 60 GyE in 30 fractions

Pre-treatment ~9 months Post-treatment

Thinking beyond protons?

Heidelberg Ion Therapy (HIT)

Advantages of Carbon Ion Therapy• Spread-Out Bragg Peak (enhanced dose distribution)

• Potential for Dose Verification via available imaging

• Superior Linear Energy Transfer (LET) - (more difficult to repair)• Significantly less affected by cell cycle position and hypoxia

• Magnetic steering of the Ion Beams (Scanning Beams)

• Less Lateral Scattering as compared to protons and photons

• Increased RBE (variable along path – increasing as approaches Bragg Peak)• Less dose to tissue proximal to target

• Ability to dose escalate in tumor

Mohamad et al. Carbon Ion Radiotherapy Review. Cancers. 2017

Fear with Carbon

= Protons

= Tumor

Cyclotron

Normal Tissue (Before the Tumor)

Normal Tissue (Beyond the Tumor)

Proton

Carbon

Scattering and precision: Protons

20 cm

Protons:220 MeV

50 mm

Scattering in tissue leads to shallowdose gradients

20 cm

C-12 ions380 MeV/u

50 mm

Scattering and precision: Carbon ions

Steep dose gradients due to lessscattering

Proton Therapy Indications

• Written to communicate when proton RT should be covered by insurance

• Two groups• Group 1: Proton RT supported• Group 2: Suitable in the context of clinical trial or multi-institutional

registry

Slide courtesy of Adam Kole

Simplified Indications for Proton RT

• Excellent candidates:

• Patients with long life expectancy

• Tumors with high chance for long-term control

• Cases which require high dose adjacent to critical structures

• Cases where reducing low-medium dose would reduce acute or late toxicity

• Poor candidates:

• Any emergent treatment

• Most metastatic or palliative cases

• Diseases with particularly poor prognosis (eg. DIPG, GBM)

Clinical Cases

Clinical Case: Brain

MacDonald, S. M., Trofimov, A., Safai, S., Adams, J., Fullerton, B., Ebb, D., . . . Yock, T. I. (2011). Proton radiotherapy for pediatric central nervous system germ cell tumors: early clinical outcomes. Int J Radiat Oncol Biol Phys, 79(1), 121-129. doi:1

Summary

• Protons kill cancer very similarly to photons

• At this point, proton beam therapy is a tool which is useful to solve a specific dosimetric problem.• Less low and moderate dose “spill”

• Theoretically better for a number of disease sites, but…

• Proton beam therapy has its own set of challenges, but this technology has and may very well continue improve over time

Special Thanks

• Dr. Adam Kole

• Dr. Rex Cardan

• Dr. Andrew McDonald

• The staff at PSI

• The staff in Heidelberg

• All the patients treated with particle/proton therapy