July 30, 2020.
In this article, it will be discussed how physics knowledge, especially advanced nuclear and particle physics, can be applied to radiotherapy for cancer treatment.
Cancer treatment with protons therapy
Cancer is abnormal cells that grow and kill the healthy cells inside our bodies. Cancer cells are very aggressive and difficult to treat, that is why it is the leading cause of death in Thailand and the world. There are several methods to treat cancer patients. Surgery is a primary method to cure cancer patients by removing the cancer cells from the infected tissue to prevent further progression. Chemotherapy is a cancer treatment using an anti-cancer drug to treat and kill cancer cells. Besides killing the specific cancer cells, the chemotherapy drug could also affect the normal cells . Radiotherapy or radiation therapy is another way to treat cancer cells by using high energy photons or X-ray beams to shrink and kill the cancer cells. For deep-seated tumors or cancer cells, the radiation will penetrate through the normal tissue and finally ionizes the tumor or cancer cells as shown in Figure 1 (left). Because of this, the normal tissue surrounding the cancer cells and the tissue or organs located after cancer cells will receive the radiation as well.
Fig. 1 The comparison of radiotherapy with X-rays (left) and proton beams (right). Image source: https://www.protominternational.com/2019/02/4-benefits-of-proton-therapy/
Currently, proton-based treatment or proton therapy is a new method to treat cancer cells that uses protons (charged particles) to irradiate the cancer cells. In Figure 1 (right), proton therapy is different from common radiotherapy with photons or X-rays. Since protons have energy and mass, when protons interact with matter, most of the energy will be deposited at the end of particle range which is known as Bragg peak. Because of Bragg's peak, the cancer cells will receive maximum ionization and surrounding healthy tissue will receive minimum ionization. Figure 2 shows the comparison of the deposited radiation dose between protons and X-rays therapy for prostate cancer. In proton therapy, the surrounding tissue received less radiation and important organs didn’t receive any radiation at all. Therefore, proton therapy is considered as a highly effective method for treating cancer especially for deep-seated cancer such as brain cancer, head and neck cancer, and also cancer cases in pediatric that must be treated carefully as well.
Sensors and Proton Imaging
In radiotherapy, the treatment plan procedure is important and needs to be performed before patients undergo radiotherapy treatment. In the treatment plan, the calculation of absorbed dose and tumor localization is performed in the treatment planning system (TPS). Tumor localization includes mapping the tumor location and size to irradiate the tumor precisely. To do tumor localization, we need a medical image or radiograph obtained from CT scans (computed tomography) or MRI scans (magnetic resonance imaging). CT scans utilize X-rays irradiation to produce medical images while an MRI scan utilizes a strong magnetic field and radio waves to produce detailed images of organs and soft tissues. Usually, CT images are used for tumor localization in the treatment plan, however, because CT images used X-rays radiation, the patients who undergo CT scan procedure will receive more radiation before they receive radiotherapy treatment.
Fig. 2 The comparison of deposited dose in proton therapy (left) and X-rays radiotherapy (right). Image source: https://www.procure.com/th/what-is-proton-therapy/
In proton therapy, CT images are also used in the treatment plan for proton therapy. However, when the Hounsfield unit (HU) is converted to density (ion-stopping power), we will have a deviation up to 3%. This deviation might cause inaccuracy in locating the tumor site and irradiate the wrong location. Researchers try to solve this issue by producing medical images using proton beams from the same source as a proton therapy machine by increasing the proton energy and reducing the proton intensity. The obtained medical images later will be reconstructed and finally, we will get CT images from proton beams which are called proton computed tomography or pCT. In 2016, professor Robert P. Johnson, a particle physicist from the University of California, USA, has created a prototype of a proton beam imaging device . The test was performed on a simulated human head phantom using a silicon particle detection system from NASA called Fermi Gamma-ray Space Telescope. The obtained result shows the radiation dose of proton imaging or pCT is 1.4 mGy which is less than conventional imaging using X-rays with a radiation dose of 30 – 50 mGy . This result also shows the possibilities and advantages of pCT.
Knowledge of nuclear and particle physics applied
The European Center for Nuclear Research, or "CERN" (CERN: is an acronym from the French language, which means Center of European Nuclear Research) located in Geneva, Switzerland, is the largest research institution in the field of nuclear and particle physics. At CERN, two protons beams have been accelerated with a velocity close to the speed of light (speed of light = 300,000,000 meters/second) and have collided. Because of this collision, protons will be scattered revealing the inner part of a proton which is believed as the smallest matter ever before this experiment took place. Many scientists hope to find new particles like the Higgs bosons which are according to the theory, there are the particles that create the mass of particles and other matter in the universe, leading to an understanding of the fundamental nature of the universe . This collision also shows the simulation of the “Bing Bang” event, generally accepted as an explosion that caused the universe some 14 billion years ago. In this experiment, the most important part is the sensor that detects the particle paths and classifies the smallest particles as fast as they have ever encountered after the collision. To be able to detect these small and fast particles, the sensor must be the most efficient and durable. Therefore, this kind of sensors has been developed and improved with the latest technology at CERN. The technology and process for creating and designing CERN's particle detection systems are considered to be the best in the world.
Fig. 3 The ALPIDE sensor is a CMOS sensor pixel with a dimension of 15x30 mm2, with a total of 524,288 pixels detecting pixels with a circular glass to prevent surface.
Suranaree University of Technology (SUT) has collaborated with A Large Ion Collider Experiment (ALICE), CERN to conduct research and test the sensor named ALPIDE (ALICE Pixel Detector), which is the latest silicon tracking sensor as shown in Figure 3. Since 2012, SUT has started the research topic in finding a suitable material for the ALPIDE sensor fabrication. After the sensor production has been completed, we have to test the performance and the efficiency of the ALPIDE sensor. Apart from being used in the particle detectors at CERN, ALPIDE sensors can also be used for other proposes such as for medical applications.
Proton imaging research in Thailand
In Thailand, Suranaree University of Technology, with supports from the Thailand Center of Excellence in Physics (ThEP) and the International Research Network (IRN), has been conducting research to develop the first pCT prototype in Thailand. The high-performance particle sensor ALPIDE from ALICE, CERN, will be employed to detect protons before and after penetrating the object. Figure 4 shows the main components of the pCT prototype system as follows:
Fig. 4 The structure of proton Computed Tomography (pCT).
Number 1: Proton detection sensors are used to detect and determine the proton's path. In constructing this detection system, it requires the knowledge and skills obtained from working with ALICE, CERN. The first prototype of pCT, we will use the ALPIDE sensor as a starting point, but later, we have a definite plan to design and fabricate a sensor within Thailand.
Number 2: Calorimeter. This part is responsible for measuring the energy of protons before and after entering the object. The obtained energies will be compared for reconstructing the images using an image reconstruction program.
Number 3: Phantom (object). It consists of materials with densities similar to the density of organs or soft tissue in the human body. Besides that, we could also use a bio-phantom filled with cells to observe the response of cells to proton irradiation and obtain the survival curve. This bio-phantom also can be used as verification tools before the pCT device will be used on humans. SUT has developed the 3D bio-phantom in collaboration with GSI Helmholtz Centre for Heavy Ion Research.
In the near future, the pCT prototype with phantom will be tested using proton beams from the proton machine at "Her Royal Highness Princess Maha Chakri Sirindhorn Proton Center (HPSP)", King Chulalongkorn Memorial Hospital. The center is expected to be operated for treatment by the end of the year 2020. The plan will be made by placing a prototype on the patient bed and irradiating protons directly. The schematic picture for the prototype testing is shown in Figure 5.
Fig. 5 Experimental setup for testing the pCT prototype.
To succeed in this pCT project, it requires knowledge and skills in many fields such as particle physics, materials science, electronics, radiobiology and computer programming. In Thailand, there are several research institutes doing research in different fields such as Thai Microelectronics Center (TMEC), which is a specialist in sensor design and production; Thailand Institute of Nuclear Technology (Public Organization) (TINT) which is a national nuclear research and development; Synchrotron Light Research Institute (Public Organization) (SLRI), an institution that deals with the use of synchrotron light from electron beams for the study of structural materials at the atomic and molecular levels; National Electronics and Computer Technology Center (NECTEC), which has the skills and capability to build the dental CT scan using X-ray. Considering the capabilities of each research institute together with Suranaree University of Technology, it is highly possible that Thailand will be able to produce pCT machines in the future.
Nowadays, cancer treatment with proton therapy is getting more popular and will spread wider in many countries in the future. Suranaree University of Technology has collaborated ALICE, CERN, resulting in knowledge and advanced technology transfer in particle detectors which can be applied in medical applications. When the pCT machine has been successfully constructed, it will able to detect cancer cells and help to treat cancer effectively. This also will ease the medical physicists and doctors because they have high-resolution tools for producing medical images used in treatment planning. Hopefully, this technology can improve the capability and quality of cancer treatment in Thailand and be able to reduce the death rate of cancer patients to the minimum. This project would undergo countless efforts and multiple-trial experiments before getting clinical approval. It might take more than 10 years to be accepted for clinical usages. But we believe that it is possible to build and deliver such a pCT machine for the betterment of cancer treatment to benefit not only Thailand but the world.
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Asst. Prof. Dr. Chinorat Kobdaj
Nuclear and Particle Physics laboratory, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand