In radiotherapy, ionizing radiation is used to cause irreparable damage to the DNA and inhibit cell cycling of the cancer cells. However, radiation does not just cause selective damage in cancerous cells but also injures healthy tissue. The biological response to radiation is quantified in terms of the relative biological effectiveness (RBE), defined as the ratio between the absorbed dose of reference radiation such as Cobalt-60 and that of test radiation for a given biological endpoint i.e. cell type, cell cycle, survival level, radiation dose, dose rate and dose per fraction. RBE does not simply depend on the mean value of energy deposition, but on its stochastic distribution, which, in turn, depends on the target size. When changing treatment from one radiation modality to another, it is important to understand the difference in RBE between the two radiation sources/modalities for the same endpoint.
In the Radiobiology and Microdosimetry group, the difference in RBE between different brachytherapy radiation sources and external beam radiotherapy modalities are investigated both experimentally through animal and cell irradiation studies and theoretically through microdosimetrical studies conducted on scanned images from patient’s histopathology slides. Combining these results and incorporating them with appropriate radiobiological models will yield a patient-specific RBE as part of a multiscale treatment planning approach.
Investigating the correlation between induction of DNA double strand breaks and size of the cell nuclei
Behnaz Behmand, Ph.D.
Dr. Behnaz Behmand is investigating the correlation between induction of DNA double strand breaks and size of the cell nuclei, DNA content and chromatin compaction in different cancer cell lines following irradiation with different radiation qualities. Results from her studies will be used to develop computational models and predict radiation induced damage, which will help us understand which patients will benefit from radiotherapy treatments with a certain radiation quality
Investigation of Diffusion of the Alpha Particle Emitting Daughters of the AlphaTau DaRT Seed Through Animal Models
Melodie Cyr, Ph.D. Student
In radiotherapy ionizing radiation is used to cause irreparable damage to the DNA and inhibit cell cycling of the cancer cells. However, radiation does not just cause selective damage in cancerous cells but also injures healthy tissue. Many strategies have been developed for delivering dose in radiotherapy to maximize the effect of radiation on tumor cells and to spare the surrounding healthy tissues. Recently a novel brachytherapy treatment option for solid tumors is being offered by the company Alpha TAU Medical Ltd. through alpha emitters released from 224Ra-loaded brachytherapy seeds. This novel technique is called diffusing alpha-emitters radiotherapy (DaRT) and delivers a lethal dose of radiation to the tumor while sparing nearby radiation sensitive healthy tissues due to the short range of alpha particles in tissue. However, currently the diffusion of the alpha emitting daughters from the 224Ra decay in different tumors is not well known. The aim of Mélodie’s project is to establish parameters for the DaRT diffusion-leakage model through animal studies.
Relative Biological Effectiveness of Different Radiation Qualities for Hela Adenocarcinoma Cells
Naim Chabaytah, M.Sc. Student
There are many various types of radiation qualities that are used in radiotherapy treatment of cancer. However, despite the same physical dose of radiation from different radiation qualities produces varying amounts of biological damage. Therefore, it is of importance to determine the amount of biological damage a radiation quality induces in different cancer cell lines.
Naim is performing cell studies on Hela adenocarcinoma cells to determine the difference in relative biological effectiveness of Iridium-192 brachytherapy source, Xoft electronic brachytherapy source and MV photons compared with 225 kVp X-rays
RBE for Rectal Cancer
Joanna Li, M.Sc.
Photon radiation qualities used in the clinic have been assumed to have a relative biological effectiveness (RBE) of 1.00 regardless of the photon energy used. Different photon energies have varying linear energy transfers which can impact cell survival. Moreover, different cancer cell types have different responses to radiation due to their intrinsic radiosensitivity.
Joanna’s project aims to characterize the RBE of clinically relevant high and low photon energies such as MV x-rays, Ir-192 brachytherapy source and Xoft electronic brachytherapy source, using 225 kVp x-rays as a reference quality. She will irradiate human colorectal cancer cell lines HCT116 and HT29 in vitro with these photon qualities, then assess cell survival using the clonogenic assay. She will compare her data with her colleagues Naim and Joud, who are conducting RBE studies using the human cervical cancer cell line HeLa and prostate cancer cell line PC3 respectively. This will help them determine how different cancer types could affect the RBE of photon qualities.
In the future, Joanna will also aim to measure the RBE of higher linear energy transfer radiation qualities such as alpha particles. In addition, she will investigate how the DNA damage response could impact RBE for a particular cancer type by irradiating HPV+ vs. HPV- human head and neck cancer cells.
Microdosimetry of Low Energy Electrons and Photons at the Cellular Level
Mirta Dumancic, Ph.D.
To Establish Correlation Between Physical Microdosimetric Quantities Such as Dose Mean Lineal Energy, Target Size and Biological Endpoints Such as DNA Double Strand Breaks in HeLa Cells Irradiated with Iridium-192 High Dose Rate Brachytherapy Source and 225kV X-Rays Proceedings Article
In: MEDICAL PHYSICS, pp. E345–E345, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.
Characterization of the Relative Biological Effectiveness of a Range of Photon Energies for Irradiation of HeLa and PC-3 Cell Lines Proceedings Article
In: MEDICAL PHYSICS, pp. E980–E980, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.
Use of the Monte Carlo Method to Relate GAFCHROMIC (R) EBT3 Film Response to Absorbed Dose for Alpha Particle Dosimetry Proceedings Article
In: MEDICAL PHYSICS, pp. 5653–5653, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.
Patient-specific microdosimetry: a proof of concept Journal Article
In: Physics in Medicine and Biology, 2021, ISSN: 1361-6560.
Correlation between Radiation-induced Foci from 192Ir Brachytherapy and Tumor Nuclei Size Presentation
World Congress of Brachytherapy (WCB) - Online, 06.05.2021.
In: Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB), vol. 81, pp. 162–169, 2021, ISSN: 1724-191X.
Patient-specific microdosimetry: a proof of concept Journal Article
In: Physics in Medicine & Biology, 2021, ISSN: 0031-9155.
Correlation Between Radiation-Induced Foci and Tumor Nuclei Size Distribution Presentation
AAPM | COMP Virtual Meeting, 12.07.2020.
Towards Patient Specific Microdosimetry Presentation
Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm Presentation
Physica Medica, 01.01.2019.
In: Physics in Medicine and Biology, vol. 63, no. 17, pp. 175007, 2018, ISSN: 1361-6560.
In: Brachytherapy, vol. 17, no. 3, pp. 634–643, 2018, ISSN: 1873-1449.
In: International Journal of Radiation Oncology, Biology, Physics, vol. 100, no. 1, pp. 270–277, 2018, ISSN: 1879-355X.
In: Physics in Medicine and Biology, vol. 62, no. 13, pp. 5495–5508, 2017, ISSN: 1361-6560.
In: Brachytherapy, vol. 16, no. 3, pp. S80, 2017, ISSN: 1538-4721, 1873-1449, (Publisher: Elsevier).
In: Brachytherapy, vol. 16, no. 3, pp. 586–596, 2017, ISSN: 1538-4721.
Resolving dosimetric issues in intravascular brachytherapy Presentation
Medical Physics, 01.01.2017.
Investigation of a New Device to Improve Dosimetric Outcomes in Intravascular Brachytherapy Presentation
Microdosimetric evaluation of intermediate-energy brachytherapy sources using Geant4-DNA Presentation
Radiotherapy and Oncology, 01.01.2017.
In: Medical Physics, vol. 43, no. 5, pp. 2131–2140, 2016, ISSN: 2473-4209, (_eprint: https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1118/1.4944870).
Impact of the microdosimetric spread on cell survival data analysis Presentation
World Congress on Medical Physics and Biomedical Engineering, 06.10.2015.
In: Radiation Protection Dosimetry, vol. 166, no. 1-4, pp. 361–364, 2015, ISSN: 1742-3406.
Influence of Proton Track-Cell Nucleus Incidence Angle On Relative Biological Effectiveness Presentation
Med. Phys., 01.01.2015.
On the Value of LET as a Radiation Quality Descriptor for RBE Presentation
AAPM annual meeting Med. Phys. 42, 3469, 01.01.2015.
Exploring RBE Dependence on Proton Track Angular Incidence Presentation
World Congress on Medical Physics and Biomedical Engineering, 01.01.2015.
Initial DNA damage patterns with MC track structure and ionization clusters Presentation
Radiotherapy and Oncology, 115, Supplement 1, S76-S77, 01.01.2015.
Impact of the microdosimetric spread on LQ-parameterization of cell survival data for protons and Co-60 photons Presentation
Radiotherapy and Oncology, 115, Supplement 1, S803, 01.01.2015.
Determining microdosimetric spread amongst cells subject to microbeam radiotherapy using Monte Carlo simulation. Micro-Mini & Nano Dosimetry and Prostate Cancer Treatment Workshop Presentation
MMND-IPCT Conference, 20.10.2014.
Calculation of microdosimetric data due to subcellular compartment sizes determined from histological samples Presentation
Radiotherapy and Oncology, 01.01.2014.