Embed Size (px)
Citation preview
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
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
