Project Title: Knowledge-based Radiation Treatment Planning for Glioblastoma Multiforme
Project Title: To be added
Project Title: Nanoparticle-aided radiation therapy with scintillating high-Z materials
Project Title: To be added .
Project Title: Development of a probe-format calorimeter for absolute clinical dosimetry of high-energy photon, electron, and proton beams
Project Title: Enhancement of texture-based metastasis prediction models via the optimization of PET/MR imaging acquisition protocols
The project involves creation of biocompatible rare earth-based nanoparticles and testing them for activity against cancer in vitro and in vivo, with or without radiation therapy.
We will develop a new kind of particle for radiosensitization of tumours by direct intratumoral or possibly intravenous injection and test them in vitro and in vivo. The particles, cerium-doped lanthanum fluoride (LaF3:Ce), are made of low-toxicity constituents and have many desirable photophysical properties compared to currently existing radiosensitizers in the field. They can radiosensitize tumours on their own via the photoelectric effect, or they may be conjugated to a photosensitizer for X-ray based singlet oxygen generation.
Additionally, software modelling and simulation of nanoparticle localization and radiation response will help corroborate the mechanisms by which the nanoparticles induce different varieties of “insults” and affect cell survival, as well as quantify dose enhancement at the nanoparticle level.
1. D.R. Cooper, D. Bekah, J.L. Nadeau, (2014) Gold Nanoparticles and Their Alternatives for Radiation Therapy Enhancement, Frontiers in Chemistry 2, Article 86, 13 pages October 2014, doi: 10.3389/fchem.2014.00086.
2. Kudinov, K, Cooper D., Tyagi P., Bekah D., Bhattacharyya D., Hill C., Kin Ha J., Nadeau J.L., Bradforth S.G. (2015), Evidence of energy transfer in nanoparticle-porphyrins conjugates for radiation therapy enhancement. Proc. SPIE 9338 Colloidal Nanoparticles for Biomedical Applications X 93380H (March 12, 2015); doi:10.1117/12.2077985.
3. Devesh Bekah, Daniel Cooper, Konstantin Kudinov, Colin Hill, Jan Seuntjens, Stephen Bradforth and Jay Nadeau (2016) Synthesis and Characterization of Biologically Stable, Doped LaF3 Nanoparticles Co-Conjugated to PEG and Photosensitizers, Journal of Photochemistry and Photobiology A: Chemistry Volume 329, 1 October 2016, Pages 26–34.
4. Cooper DR , Capobianco JA , Seuntjens J (2018) Radioluminescence studies of colloidal oleate-capped β-Na(Gd,Lu)F4:Ln3+ nanoparticles (Ln = Ce, Eu, Tb), Nanoscale 2018 Apr 26;10(16):7821-7832. doi: 10.1039/c8nr01262h.
5. Kudinov KA, Cooper DR, Ha JK, Hill CK, Nadeau JL, Seuntjens JP, Bradforth SE (2018) Scintillation Yield Estimates of Colloidal Cerium-Doped LaF3 Nanoparticles and Potential for “Deep PDT”, Radiat Res. 2018 Apr 19. doi: 10.1667/RR14944.1. [Epub ahead of print].
Purpose: To create a knowledge-based radiation treatment planning model for brain tumor patients, specifically Glioblastoma multiforme (GBM), using RapidPlan, a commercially available product. Methods and Materials: The model predicts achievable dose sparing for organs at risk (OARs) using a library of 82 inverse treatment plans, and provides optimization objectives to be used for treatment planning. The model is then validated on an independent set consisting of 45 patients. Results: The plans created by the model are clinically acceptable, having slightly improved planning target volume (PTV) coverage (ΔD98% = 0.5 Gy) and slightly lower mean doses to the optic apparatus (1.5 Gy) and eye (0.6 Gy). The planning time can be as low as 7 minutes, compared to about two hours for planning without RapidPlan. Conclusions: Knowledge-based planning model for GBM delivers quick, high-quality plans for a diverse set of patients.
1. André Diamant, Avishek Chatterjee, Sergio Faria, Issam El Naqa, Houda Bahig, Edith Filion, Cliff Robinson, Hani Al-Halabi, Jan Seuntjens (2018) Can dose outside the PTV influence the risk of distant metastases in stage I lung cancer patients treated with stereotactic body radiotherapy (SBRT)?, Radiotherapy and Oncology, Available online 2018 May 22. doi.org/10.1016/j.radonc.2018.05.012. [Epub ahead of print].
2. Avishek Chatterjee, PhD, Monica Serban, MSc, Bassam Abdulkarim, MD, PhD, Valerie Panet-Raymond, MD, Luis Souhami, MD, FASTRO, George Shenouda, MBBCh, PhD, FRCP (C), Siham Sabri, PhD, Bertrand Jean-Claude, PhD, Jan Seuntjens, PhD (2017) Performance of Knowledge-Based Radiation Therapy Planning for the Glioblastoma Disease Site, International Journal of Radiation Oncology • Biology • Physics 99(4): 1021-1028.
Our work involves the development of an innovative probe-format calorimeter (Arrow) for clinical dosimetry. Calorimetry-based detectors are unique in that no radiation is required for calibration and thus offer the most absolute method to measure dose. Calorimeters have been used by standards laboratories for decades, however these calorimeters are too bulky and technically cumbersome for routine clinical use. The enhancement of our unique GPC design will be more compact and simple to operate than prior art. With a number of prototypes and experimental studies suggesting the feasibility of the technology, and the backing of an industry partner, the objective is to further refine and validate this cutting edge device for end-user testing and eventual commercialization .
1) Renaud J, Sarfehnia A, Marchant K, McEwen M R, Ross C, Seuntjens J P (2015) Direct measurement of electron beam quality conversion factors using water calorimetry, Med. Phys. 42(11):6357-6368.
2) James Renaud, A. Sarfehnia, J. Seuntjens (2016) Experimental benchmarking of a probe-format calorimeter for use as an absolute clinical dosimeter, ESTRO 35 Conference 2016, April 29 to May 3, 2016, Turin, Italy. One of the five abstracts that was selected out of the numerous submitted under physics track – publication of the conference report (conference paper).
3) Renaud J, Rossomme S, Sarfehnia A, Vynckier S, Palmans H, Kacperek A, Seuntjens J (2016) Development and application of a water calorimeter for the absolute dosimetry of short-range particle beams, Phys Med Biol. 2016 Sep 21;61(18):6602-6619.
4) James Renaud, Arman Sarfehnia, Julien Bancheri, Jan Seuntjens (2017) Aerrow: A probe-format graphite calorimeter for absolute dosimetry of high-energy photon beams in the clinical environment, Med Phys 45(1):414-428, January 2018; DOI: 10.1002/mp.12669. 0094-2405/2018/45(1)/414/15.
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1. Collins-Fekete C-A, Plamondon M, Martin A-G, Vigneault É, Verhaegen F, Beaulieu L. (2014) Quantifying the effect of seed orientation in postplanning dosimetry of low-dose-rate prostate brachytherapy, Med. Phys. 41, 101704.
2. Collins-Fekete C-A, Plamondon M, Martin A-G, Vigneault É, Verhaegen F, Beaulieu L. (2015) Calcifications in low-dose rate prostate seed brachytherapy treatment: post-planning dosimetry and predictive factors, Radiotherapy Oncology. 114(3):339-44.
3. Collins-Fekete C-A, Dias M.F., Doolan P., Beaulieu L., Seco J. (2015) Developing a phenomenological model of the proton trajectory within a heterogeneous medium required for proton imaging, Physics in Medicine and Biology 60(13): 5071-5082.
4. Charles-Antoine Collins-Fekete, Sébastien Brousmiche, Stephen K N Portillo, Luc Beaulieu and Joao Seco (2016) A maximum likelihood method for high resolution proton radiography/proton CT, Physics in Medicine and Biology 61(23) November 3, 2016.
In our ongoing work, we have shown that texture analysis of combined FDG-PET/MR information has the potential to predict the risk of metastases to the lungs in soft-tissue sarcomas (STS), an aggressive type of cancer with high metastatic potential that develops in connective tissues of the body. However, recent studies demonstrate that acquisition mode (acquisition time, 2D or 3D acquisition) and reconstruction parameter (algorithm, iterations, filters) variations in FDG-PET imaging, and pulse sequence and acquisition parameter (e.g., TR, TE, flip angle) variations in MRI affect the expected discriminating power of the texture analysis. Therefore, our working hypothesis is that the optimization of FDG-PET and MRI protocols will further improve the discriminating power of the combined PET/MRI texture features for the prediction of lung metastases in STS cancer.
The methodology of the project is as follows. Digital tumor models will be constructed from FDG-PET and MRI clinical imaging datasets of 30 STS tumors. Guidelines from the literature will be followed in order to build the FDG-PET and MRI digital tumor models from clinical data. In collaboration with the Montreal Neurological Institute, we will develop more complex algorithms to preserve the (texture) heterogeneity characteristics of FDG-PET and MRI tumors in the models. Finally, digital tumor models will be incorporated into digital human anthropomorphic phantoms from the XCAT series and an in-house PET/MRI simulation platform will be used to optimize FDG-PET and MRI image acquisition protocols to produce images with the optimal representation of textural features necessary to improve lung metastases prediction in STS cancer. Overall, this multidisciplinary endeavour could potentially impact the personalization of cancer treatments and hence improve patients’ outcomes.
1) Martin Vallières†, Monica Serban, Ibtissam Benzyane, Zaki Ahmed, Shu Xing, Issam El Naqa, Ives R. Levesque, Jan Seuntjens, Carolyn R. Freeman (2018) Investigating the role of functional imaging in the management of soft-tissue sarcomas of the extremities, Physics and Imaging in Radiation Oncology 6: 53-60.
2) Martin Vallières†, Emily Kay-Rivest, L´eo Jean Perrin, Xavier Liem, Christophe, Furstoss, Hugo J. W. L. Aerts, Nader Khaouam, Phuc Felix Nguyen-Tan, Chang-Shu Wang, Khalil Sultanem, Jan Seuntjens & Issam El Naqa (2017) Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer, Sci Rep 7(1):10117. Epub 2017 Aug 31.
3) 680 Martin Vallières, Sébastien Laberge, André Diamant and Issam El Naqa (2017) Enhancement of multimodality texture- based prediction models via optimization of PET and MR image acquisition protocols: a proof of concept, Phys. Med. Biol. 62: 8536–8565.