Radiation Therapy: Translating Basic Physics Research into Oncology
Medical Devices
2/17/2025
My Motivation to Investigate this Topic
My journey began with a deep fascination for nuclear structure physics, particularly the study of nuclear excitation via particle accelerators and the precise spectroscopy of gamma-ray emissions to unravel the quantum structure of nuclei.
For years, as part of large, international research collaborations, I investigated how ionizing radiation interacts with matter, probing energy levels and decay pathways in isotopes like cadmium-110 and iridium-179. This research instilled in me an appreciation for its potential for controlled, purposeful application.
Over the past 29 years in the medical device industry, I’ve been participating in translating innovations emerging from physics into clinical tools - whether diagnosing cancer tissue with CT or providing mechanical bone fixation through suitable implants.
The synergy between basic nuclear physics research and medical needs in oncology is profound. My career bridges two worlds: the abstract rigor of nuclear physics and the tangible impact of medical technology. By exploring how basic research has catalyzed breakthroughs like particle therapy or radiopharmaceuticals, I aim to highlight the human value of fundamental science.
Yet, I’ve often wondered: How have foundational discoveries in nuclear physics directly shaped modern targeted cancer therapies?
Different Modes of Radiation Therapy
X-Ray Therapy
Linear Accelerators (LINACs) produce X-rays by accelerating electrons to high speeds using radiofrequency waves. These electrons are then directed at a metal target (e.g. tungsten), converting their kinetic energy into X-rays.
Interaction of X-Ray Photons with Matter
The interaction of X-ray photons with matter occurs primarily through four mechanisms:
- photoelectric effect
- Compton scattering
- coherent scattering
- pair production
In X-ray superficial therapy (e.g. skin tumor), the beam energy can be 20-150 keV, whereas for deeper tumors the X-ray energy from LINACs can be 4 MeV or higher. Assuming the tumor tissue predominantly has carbon, nitrogen, and oxygen as tissue material (Z = 6, 7, 8), we can look at the probabilities of interaction between X-Rays (as a certain type of photon) and material.
The probability of the photoelectric effect interaction is inversely proportional to the cube of the photon energy (E) and directly proportional to the cube of the atomic number (Z) of the material:
Pₚₕₒₜₒ∝Z³/E³
Compton scattering, on the other hand, involves the scattering of an X-ray photon by a free or loosely bound electron, resulting in a scattered photon and a recoiling electron, with a probability that is close to linear with Z, or more precisely to the number of electrons per unit mass. In X-ray therapy, a beam energy in the range of a couple of MeV makes Compton scattering highly probable as an energy deposit mode in tumor tissue.
Coherent scattering, also known as Rayleigh scattering, is a type of interaction where a photon scatters off the electrons of an atom without transferring energy to them. Coherent scattering, in the first approximation, follows a probability dependence of Z²/E². Coherent scattering is more significant at lower photon energies (e.g., 30-50 keV) and decreases with increasing energy. At higher energies of 100-1000 keV, Compton scattering becomes more dominant.
Pair production occurs when a high-energy photon interacts with the electromagnetic field of a nucleus, resulting in the creation of an electron-positron pair. This process is possible only at photon energies above 1.022 MeV and is more probable in materials with high atomic numbers (Z), which are not very abundant in tissue tumor.
Shaping the X-Ray Beam to Match the Tumor
The X-ray beam is shaped and directed by a multi-leaf collimator, which consists of numerous thin leaves that can move independently to create complex beam profiles. This allows for precise targeting of tumors while sparing surrounding healthy tissue.
The shaped beam is delivered to the tumor site with high accuracy, typically within a 2 mm margin, ensuring that the radiation dose is concentrated on the tumor while minimizing exposure to normal tissue.
Product examples are Varian’s TrueBeam or Elekta’s Versa HD.
Proton Therapy
Instead of photons, it is possible to use particles as the treatment delivery mechanism. Proton is one example, electrons another (in form of beta particles).
My early studies of particle interactions and Bragg peak physics mirror the principles behind proton beam delivery systems like Proteus ONE by IBA. The physics governing a precise energy deposit to a narrowly defined tumor volume is based on the interaction between protons at a particular kinetic energy and the type of material. The clinical solution makes use of the Bragg peak occurring at a specific depth within the body of the patient.
A specific formula for the Bragg peak (shown in the image above) is not straightforward, as it involves complex calculations of energy loss and stopping power. However, the Bragg peak can be approximated as a function of the proton's initial energy and the material's properties.
The peak occurs at a depth where the proton's velocity is minimal, and its energy loss is maximal. The energy loss per unit distance (dE/dx) increases as the proton slows down, peaking at the end of its range, giving the typical peak to the far right of the curve displayed in green color.
Proton therapy is ideal for tumors close to sensitive brain structures, reducing the risk of cognitive impairment or secondary malignancies. Another target is the Base-of-Skull tumors to help preserve vital structures like the optic nerves and brainstem.
Prompt Gamma Timing is a technique used in proton therapy to verify the range of therapeutic proton beams in real-time, by measuring the time distribution of prompt gamma rays emitted when protons interact with tissue.
Radiopharmaceuticals / Beta-Emitting Therapy
My work with gamma-ray spectroscopy parallels today’s use of isotopes for targeted Beta Therapy. The decay chains I once mapped in lab experiments now offer therapies like Pluvicto (Novartis), used for prostate-specific membrane antigen (PSMA)-positive cells in prostate cancer through radioactive decay.
It is a beta-emitting radioligand therapy that uses lutetium-177 to target prostate-specific membrane antigen (PSMA)-positive cells in prostate cancer through the decay of radioactive lutetium-177, which constitutes 71 protons and 106 neutrons, to give a mass number of 177. The decay with a half-life of 6.6 days can be depicted as follows:
177Lu → 177Hf +β⁻ + antineutrino
The beta emission β⁻ is what delivers the therapeutic effect by damaging the DNA of PSMA-positive cancer cells.
Boron Neutron Capture Therapy
>Boron Neutron Capture Therapy is a specialized form of radiation therapy that does not fit as a first-line treatment for most cancers but offers a unique approach for certain types of malignant tissue that are adjacent to very sensitive healthy tissue, such as for aggressive brain or neck tumor or meningioma. It is primarily considered for cancers where conventional therapies have limitations or have failed.
10B + n → 7Li + 4He + 2.79 MeV
A boron-containing compound is selectively delivered through intravenous or direct injection to the tumor cells. Thermal neutrons are used because they have a high probability of being captured by boron-10 due to their low energy.
In the reaction helium-4 is created, also called alpha particle. This reaction releases a total of 2.79 MeV of energy, which is deposited locally within the tumor cells, causing damage to their DNA and leading to cell death.
The alpha particles have a short range (about 5-9 μm), ensuring that most of the energy is deposited within the tumor cells, minimizing damage to surrounding healthy tissue.
Neutron Therapeutics is a leading developer of accelerator-based neutron systems for BNCT. Their nuBeam platform is designed to provide a compact, in-hospital neutron source, replacing traditional nuclear reactors.
Why Radiation Works Against Cancer
Radiation therapy (RT) harnesses ionizing radiation—high-energy particles or waves (e.g., X-rays, protons, alpha or beta particles)—to damage cancer cell DNA, causing lethal double-strand or single-strand breaks. Cancer cells, which divide rapidly and lack robust repair mechanisms, are more vulnerable to this damage than healthy tissue. RT leverages two mechanisms:
- Direct ionization: Radiation directly breaks DNA bonds.
- Indirect ionization: Generates reactive oxygen species that oxidize DNA. Modern RT balances tumor eradication with sparing healthy tissue, enabled by precision technologies.
The Role of CT in Radiation Therapy
As a clinical scientist in Computed Tomography (CT), I have had extensive experience with another clinical application of X-rays interacting with matter. In CT, the energy domain typically ranges from 100 to 150 keV, where the photoelectric effect plays a significant role.
This interaction is crucial for creating the diagnostic contrast necessary for tissue delineation, allowing for clear visualization of anatomical structures. Moreover, CT plays a pivotal role in radiation treatment planning, providing precise anatomical information that is essential for accurately targeting tumors while sparing surrounding healthy tissues.
Pre-Treatment Planning
CT scans help accurately define the gross tumor volume and planning target volume, ensuring precise targeting of the tumor while minimizing exposure to healthy tissues. CT images allow for precise delineation of critical structures (e.g., spinal cord, lungs) to avoid excessive radiation exposure.
CT data provide Hounsfield units (HU), which quantify the linear attenuation coefficient of X-rays in various materials. These HU values can be used to estimate electron density indirectly through CT-electron density (CT-ED) calibration curves.
This process is crucial for accurate dose calculations in radiation therapy, ensuring that the planned dose is delivered precisely to the tumor. To achieve this, CT scans are typically performed with the patient in the treatment position, ensuring that the anatomy is accurately represented as it will be during therapy. This alignment is essential for minimizing discrepancies between planning and actual treatment delivery.
Intra-Treatment Verification
Image-Guided Radiotherapy utilizes cone-beam CT to verify the position of the tumor and surrounding structures at the time of treatment, allowing for real-time adjustments to ensure accurate delivery of radiation.
CT scans help account for patient motion during treatment, enabling adjustments to maintain precise targeting.
Intra-treatment CT scans can be used to adapt treatment plans if anatomical changes occur during therapy, ensuring that the tumor remains adequately targeted while sparing healthy tissues.
Conclusion
As we explore the intersection of physics and medicine in cancer treatment, it becomes clear that advancements in radiation therapy are deeply rooted in fundamental scientific discoveries. From the precise delivery of X-rays via LINACs to the targeted action of proton therapy and radiopharmaceuticals, each modality leverages unique physical principles to combat cancer.
The journey from basic research to clinical application is exemplified by technologies like Boron Neutron Capture Therapy, which harnesses the power of neutron capture to selectively destroy tumor cells. Meanwhile, innovations in imaging, such as CT scans, play a crucial role in treatment planning and verification, ensuring that radiation is delivered with maximum precision.
As a medical device expert and nuclear physicist, I've witnessed firsthand how the synergy between these fields can lead to groundbreaking treatments. The future of cancer therapy will undoubtedly involve further integration of physics and medicine, driving the development of more effective, targeted, and personalized treatments.
By continuing to bridge the gap between scientific inquiry and clinical practice, we can unlock new possibilities for cancer care, offering hope to patients and families worldwide. As we move forward, it's essential to recognize the human value of fundamental science and its potential to transform lives through innovative medical technologies.
Go back