Radiobiology and Microdosimetry

Mission

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.

Members

Behnaz
Melodie
Naim
Joanna
Mirta

Projects

Investigating the correlation between induction of DNA double strand breaks and size of the cell nuclei

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 Mèlodie’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.

Joanna is working on measuring the RBE of different radiation qualities for human rectal cancer cell lines.

Microdosimetry of Low Energy Electrons and Photons at the Cellular Level

Mirta Dumancic, Ph.D.

Microdosimetry is a powerful tool to explore and correlate radiobiological effects with fundamental energy depositions on a cellular level. By using the histopathological data from patients to characterize the tumor morphology, we can use currently available track-structure Monte Carlo codes to investigate the energy depositions inside the cell nuclei and their correlations with in-vitro cell survival data and more importantly, the ultimate treatment outcomes in patients. In our studies, we focus on low-energy electron and photon radiation sources in order to further the clinical practice toward patient-specific treatment planning. By using both Geant4 simulation techniques and available experimental tools to measure microdosimetric distributions, we aim to provide a more quantitative understanding of the radiobiological effects for these widely-used sources. 
 

Publications

2022

Dev, Sachin; Behmand, Behnaz; Pater, Piotr; Enger, Shirin A.

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 Inproceedings

In: MEDICAL PHYSICS, pp. E345–E345, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.

BibTeX

Babik, Joud; Chabaytah, Naim; Behmand, Behnaz; Connell, Tanner; Evans, Michael; Ruo, Russell; Poirier, Y; Enger, Shirin A.

Characterization of the Relative Biological Effectiveness of a Range of Photon Energies for Irradiation of HeLa and PC-3 Cell Lines Inproceedings

In: MEDICAL PHYSICS, pp. E980–E980, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.

BibTeX

Martinez, Victor Daniel Diaz; Cyr, Melodie; Slobodan, Devic; Tomic, Nada; Lewis, David F; Enger, Shirin A.

Use of the Monte Carlo Method to Relate GAFCHROMIC (R) EBT3 Film Response to Absorbed Dose for Alpha Particle Dosimetry Inproceedings

In: MEDICAL PHYSICS, pp. 5653–5653, WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA 2022.

BibTeX

2021

DeCunha, Joseph M.; Villegas, Fernanda; Vallières, Martin; Torres, Jose; Camilleri-Broët, Sophie; Enger, Shirin A.

Patient-specific microdosimetry: a proof of concept Journal Article

In: Physics in Medicine and Biology, 2021, ISSN: 1361-6560.

Abstract | Links | BibTeX

Behmand, Behnaz; Evans, Michael D. C.; Kamio, Yuji; Enger, Shirin A.

Correlation between Radiation-induced Foci from 192Ir Brachytherapy and Tumor Nuclei Size Presentation

World Congress of Brachytherapy (WCB) - Online, 06.05.2021.

BibTeX

DeCunha, Joseph M.; Poole, Christopher M.; Vallières, Martin; Torres, Jose; Camilleri-Broët, Sophie; Rayes, Roni F.; Spicer, Jonathan D.; Enger, Shirin A.

Development of patient-specific 3D models from histopathological samples for applications in radiation therapy Journal Article

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.

Abstract | Links | BibTeX

DeCunha, Joseph M.; Villegas, Fernanda; Vallières, Martin; Torres, Jose; Camilleri-Broët, Sophie; Enger, Shirin A.

Patient-specific microdosimetry: a proof of concept Journal Article

In: Physics in Medicine & Biology, 2021, ISSN: 0031-9155.

Abstract | Links | BibTeX

2020

Behmand, Behnaz; Kamio, Yuji; Evans, Michael D. C.; Enger, Shirin A.

Correlation Between Radiation-Induced Foci and Tumor Nuclei Size Distribution Presentation

AAPM | COMP Virtual Meeting, 12.07.2020.

BibTeX

2019

DeCunha, Joseph M.; Villegas, Fernanda; Vallières, Martin; Camilleri-Broët, Sophie; Enger, Shirin A.

Towards Patient Specific Microdosimetry Presentation

MCMA, 19.06.2019.

BibTeX

Famulari, Gabriel; Pater, Piotr; Enger, Shirin A.

Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm Presentation

Physica Medica, 01.01.2019.

BibTeX

2018

Famulari, Gabriel; Renaud, Marc-André; Poole, Christopher M.; Evans, Michael D. C.; Seuntjens, Jan; Enger, Shirin A.

RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy applications Journal Article

In: Physics in Medicine and Biology, vol. 63, no. 17, pp. 175007, 2018, ISSN: 1361-6560.

Abstract | Links | BibTeX

DeCunha, Joseph M.; Enger, Shirin A.

A new delivery system to resolve dosimetric issues in intravascular brachytherapy Journal Article

In: Brachytherapy, vol. 17, no. 3, pp. 634–643, 2018, ISSN: 1873-1449.

Abstract | Links | BibTeX

Famulari, Gabriel; Pater, Piotr; Enger, Shirin A.

Microdosimetric Evaluation of Current and Alternative Brachytherapy Sources-A Geant4-DNA Simulation Study Journal Article

In: International Journal of Radiation Oncology, Biology, Physics, vol. 100, no. 1, pp. 270–277, 2018, ISSN: 1879-355X.

Abstract | Links | BibTeX

2017

Famulari, Gabriel; Pater, Piotr; Enger, Shirin A.

Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm Journal Article

In: Physics in Medicine and Biology, vol. 62, no. 13, pp. 5495–5508, 2017, ISSN: 1361-6560.

Abstract | Links | BibTeX

DeCunha, Joseph M.; Enger, Shirin A.

Investigation of a New Device to Improve Dosimetric Outcomes in Intravascular Brachytherapy Journal Article

In: Brachytherapy, vol. 16, no. 3, pp. S80, 2017, ISSN: 1538-4721, 1873-1449, (Publisher: Elsevier).

Abstract | Links | BibTeX

DeCunha, Joseph M.; Janicki, Christian; Enger, Shirin A.

A retrospective analysis of catheter-based sources in intravascular brachytherapy Journal Article

In: Brachytherapy, vol. 16, no. 3, pp. 586–596, 2017, ISSN: 1538-4721.

Abstract | Links | BibTeX

DeCunha, Joseph M.; Enger, Shirin A.

Resolving dosimetric issues in intravascular brachytherapy Presentation

Medical Physics, 01.01.2017.

BibTeX

DeCunha, Joseph M.; Enger, Shirin A.

Investigation of a New Device to Improve Dosimetric Outcomes in Intravascular Brachytherapy Presentation

Brachytherapy, 01.01.2017.

BibTeX

Famulari, Gabriel; Pater, Piotr; Enger, Shirin A.

Microdosimetric evaluation of intermediate-energy brachytherapy sources using Geant4-DNA Presentation

Radiotherapy and Oncology, 01.01.2017.

BibTeX

2016

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan; Naqa, Issam El

Proton and light ion RBE for the induction of direct DNA double strand breaks Journal Article

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).

Abstract | Links | BibTeX

2015

Bäckstöm, Gloria; Villegas, Fernanda; Enger, Shirin A.; Ahnesjö, Anders

Impact of the microdosimetric spread on cell survival data analysis Presentation

World Congress on Medical Physics and Biomedical Engineering, 06.10.2015.

BibTeX

Poole, Christopher M.; Ahnesjö, Anders; Enger, Shirin A.

Determination of subcellular compartment sizes for estimating dose variations in radiotherapy Journal Article

In: Radiation Protection Dosimetry, vol. 166, no. 1-4, pp. 361–364, 2015, ISSN: 1742-3406.

Abstract | Links | BibTeX

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan; Naqa, Issam El

Influence of Proton Track-Cell Nucleus Incidence Angle On Relative Biological Effectiveness Presentation

Med. Phys., 01.01.2015.

BibTeX

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan; Naqa, Issam El

On the Value of LET as a Radiation Quality Descriptor for RBE Presentation

AAPM annual meeting Med. Phys. 42, 3469, 01.01.2015.

BibTeX

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan

Exploring RBE Dependence on Proton Track Angular Incidence Presentation

World Congress on Medical Physics and Biomedical Engineering, 01.01.2015.

BibTeX

Pater, Piotr; Bäckstöm, Gloria; Villegas, Fernanda; Ahnesjö, Anders; Enger, Shirin A.; Seuntjens, Jan

Initial DNA damage patterns with MC track structure and ionization clusters Presentation

Radiotherapy and Oncology, 115, Supplement 1, S76-S77, 01.01.2015.

BibTeX

Villegas, Fernanda; Bäckstöm, Gloria; Enger, Shirin A.; Ahnesjö, Anders

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.

BibTeX

2014

Poole, Christopher M.; Enger, Shirin A.; Crosbie, Jeffrey C

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.

BibTeX

Poole, Christopher M.; Ahnesjö, Anders; Enger, Shirin A.

Calculation of microdosimetric data due to subcellular compartment sizes determined from histological samples Presentation

Radiotherapy and Oncology, 01.01.2014.

BibTeX