Alejandro Bertolet, Ph.D.

Lab Head / Assistant Professor of Radiation Oncology

About me: I am an Assistant Professor at the Massachusetts General Hospital (MGH), working in the division of Physics within the Radiation Oncology Department, led by Dr. Harald Paganetti, a world-class researcher in Radiation Oncology. Before my current position at the Massachusetts General Hospital, I completed my Ph.D. thesis in two years at the Universidad de Sevilla (Spain) and the University of Pennsylvania. During that time, I published 14 articles as the first author, most of them in prestigious journals in the Medical Physics field. I obtained an Extraordinary Doctorate Award for the exceptional quality of my Ph.D. thesis from the Universidad de Sevilla. After completing a 3-year residency program at the Hospital Virgen Macarena (Seville, Spain), I am also a certified Medical Physicist in Spain. The Radiation Research Society has recently awarded me the prestigious Jack Fowler award in recognition of my contributions to the radiation biology field.

Research Interests: My work focuses on dosimetry for radiopharmaceutical therapy (RPT) and biophysical modeling of the effects of ionizing radiation in general, with particular emphasis on multi-scale biophysical studies using the Monte Carlo technique. I am a member of the TOPAS and the TOPAS-nBio collaborations, which reunites investigators from 4 different institutions and emphasizes the development of computational tools to address medical physics and radiobiology studies. I received a K99/R00 career development award from the National Cancer Institute (NIH/NCI K99CA267560). This award has allowed me to start a new lab focusing on applications and dosimetry of novel RPT treatments. My lab already has a postdoctoral fellow and a rotating population of 3-5 visiting students from other institutions. We have recently published several articles highlighting our progress in radiobiological modeling and developing novel methods to perform dosimetry in RPT.

Awards and Honors

  • 2024 – John D. Boice Award by the National Council on Radiation Protection and Measurements
  • 2024 – Selected to the Emerging Leaders of Academic Medical Physics by the University of Wisconsin-Madison
  • 2024 – Featured as Global Rising Star by the AAPM Global Research and Scientific Innovation Committee
  • 2024 – Nominated for the MGH Center for Faculty Development Rising Mentor Award
  • 2023 – ‘One to Watch’ in 2023, Society of Nuclear Medicine and Molecular Imaging
  • 2023 – Selected as Mentor for the Summer Fellowship Program by the American Association of Physicists in Medicine
  • 2023 – Early Career Investigator Travel Award by the Radiation Research Society
  • 2022 – Andrew L. Warshaw, M.D., Institute for Pancreatic Cancer Research Fellow
  • 2022 – Loeffler Team Science Seed Funding Program Recipient by the Department of Radiation Oncology at Mass General Hospital
  • 2022 – Extraordinary Ph.D. Award by the University of Sevilla
  • 2022 – Jack Fowler Award by the Radiation Research Society
  • 2021 – Selected for the Leadership Development Program for Researchers organized by the Mass General Hospital and Harvard Medical School
  • 2021 – Invited to the World Laureates Forum
  • 2019 – Best article of the month at the University of Sevilla

Publications

  • Kunz L, Bosque JJ, Nikmaneshi M, Chamseddine I, Munn LL, Schuemann J, Paganetti H, Bertolet A. AMBER: A Modular Model for Tumor Growth, Vasculature and Radiation Response. Bull Math Biol. 2024 Oct 26; 86(12):139. https://doi.org/10.1007/s11538-024-01371-4
  • Huesa-Berral C, Terry JF, Kunz L, Bertolet A. Sequencing microsphere selective internal radiotherapy after external beam radiotherapy for hepatocellular carcinoma: proof of concept of a synergistic combination. British Journal of Radiology. 2024. https://doi.org/10.1093/bjr/tqae209
  • Chamseddine I, Shah K, Lee H, Ehret F, Schuemann J, Bertolet A, Shih HA, and Paganetti H. “Decoding Patient Heterogeneity Influencing Radiation-Induced Brain Necrosis.” Clinical Cancer Research, August 6, 2024. https://doi.org/10.1158/1078-0432.CCR-24-1215.
  • Bobić, M, Huesa-Berral C, Terry JF, Kunz LV, Schuemann J, Fisher DR, Maitz C, and Bertolet A. “Monte Carlo Dosimetric Analyses on the Use of 90 Y-IsoPet Intratumoral Therapy in Canine Subjects.” Physics in Medicine & Biology, July 25, 2024. https://doi.org/10.1088/1361-6560/ad67a4.
  • Meyer, I, Peters N, Tamborino G, Lee H, Bertolet A, Faddegon B, Mille M, Lee C, Schuemann J, and Paganetti H. “A Framework for In-Field and out-of-Field Patient Specific Secondary Cancer Risk Estimates from Treatment Plans Using the TOPAS Monte Carlo System.” Physics in Medicine & Biology, July 17, 2024. https://doi.org/10.1088/1361-6560/ad64b6.
  • Huesa-Berral C, Withrow JD, Dawson RJ, Beekman C, Bolch WE, Paganetti H, Wehrenberg-Klee E, and Bertolet A. “MIDOS: A Novel Stochastic Model towards a Treatment Planning System for Microsphere Dosimetry in Liver Tumors.” European Journal of Nuclear Medicine and Molecular Imaging 51, no. 6 (May 2024): 1506–15. https://doi.org/10.1007/s00259-023-06567-9.
  • Diaz Garcia-Prada C, Carmes L, Atis S, Parach A, Bertolet A, Jarlier M, Poty S, Garcia-Suarez D, Shin WG, Du Manoir S, Schuemann J, Tillement O, Lux F, Constanzo J, Pouget JP. Gadolinium-based nanoparticles sensitize ovarian peritoneal carcinomatosis to targeted radionuclide therapy. J Nuc Med. 2023 Oct 19; Ahead of print, https://doi.org/10.2967/jnumed.123.265418
  • Bertolet A, Chamseddine I, Paganetti H, Schuemann J. The complexity of DNA damage by radiation follows a Gamma distribution: insights from the Microdosimetric Gamma Model. Frontiers in Oncology 2023, 13, p. 1196502. https://doi.org/10.3389/fonc.2023.1196502.
  • Suárez-García D, Cortés-Giraldo MA, Bertolet A. A systematic analysis of the particle irradiation data ensemble in the key of the microdosimetric kinetic model: Should clonogenic data be used for clinical relative biological effectiveness? Radiotherapy and Oncology, 2023, 185, p. 109730. https://doi.org/10.1016/j.radonc.2023.109730.
  • Zhang Q, Gerweck LE, Cascio EW, Gu L, Yang Q, Dong X, Huang P, Bertolet A, Nesteruk KP, Sung W, McNamara AL, Schuemann J. Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine. Cancers 2023, 15(8), 2269, https://doi.org/10.3390/cancers15082269
  • Bobić M, Lalonde A, Nesteruk KP, Lee H, Nenoff L, Gorissen BL, Bertolet A, Busse PM, Chan AW, Winey BA, Sharp GC, Verburg JM, Lomax AJ, Paganetti H. Large anatomical changes in head-and-neck cancers – a dosimetric comparison of online and offline adaptive proton therapy. Clinical and Translational Radiation Oncology. 31 March 2023, 100625. https://doi.org/10.1016/j.ctro.2023.100625
  • Zhang Q, Gerweck LE, Cascio EW, Yang Q, Huang P, Niemierko A, Bertolet A, Nesteruk KP, McNamara AL, Schuemann J. Proton FLASH effects on mouse skin at different oxygen tensions. Phys Med Biol. 2023 Feb 2. PMID: 36731139, https://doi.org/10.1088/1361-6560/acb888
  • Bertolet A, Ramos-Méndez J, McNamara A, Yoo D, Ingram S, Henthorn N, Warmenhoven JW, Faddegon B, Merchant M, McMahon S, Paganetti H, Schuemann J. Impact of DNA geometry and scoring on Monte Carlo track-structure simulations of initial radiation-induced damage. Radiation Research. 2022; 198(3):207-22. https://doi.org/10.1667/RADE-21-00179.1
  • Miras H, Terrón JA, Bertolet A, Leal A. Modified Geometry of 106Ru Asymmetric Eye Plaques to Improve Dosimetric Calculations in Ophthalmic Brachytherapy. J Pers Med. 2022 Apr 29;12(5). PMID: 35629144, PMCID: PMC9144752, https://doi.org/10.3390/jpm12050723
  • Bertolet A, Abolfath R, Carlson DJ, Lustig RA, Hill-Kayser C, Alonso-Basanta M, Carabe A. Correlation of LET With MRI Changes in Brain and Potential Implications for Normal Tissue Complication Probability for Patients With Meningioma Treated With Pencil Beam Scanning Proton Therapy. Int J Radiat Oncol Biol Phys. 2022 Jan 1;112(1):237-246. https://doi.org/10.1016/j.ijrobp.2021.08.027
  • Bertolet A, Wehrenberg-Klee E, Bobic M, Grassberger C, Perl J, Paganetti H, Schuemann J. Pre- and post-treatment image-based dosimetry in90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit. Phys Med Biol. 2021; 66 244002. https://doi.org/10.1088/1361-6560/ac43fd
  • Baratto-Roldán A, Bertolet A, Baiocco G, Carabe A, Cortés-Giraldo MA. Microdosimetry and dose-averaged LET calculations of protons in liquid water: a novel Geant4-DNA application. Frontiers in Physics. 2021 Oct 27 9:726787. https://doi.org/10.3389/fphy.2021.726787
  • Miras Del Río H, Ortiz Lora A, Bertolet Reina A, Terrón León JA. A Monte Carlo dose calculation system for ophthalmic brachytherapy based on a realistic eye model. Med Phys. 2021 Aug;48(8):4542-4559. PMID: 34250607, https://doi.org/10.1002/mp.15045
  • Bertolet A, Ramos-Méndez J, Paganetti H, Schuemann J. The relation between microdosimetry and induction of direct damage to DNA by alpha particles. Phys Med Biol. 2021 Jul 30;66(15). PMID: 34280910, PMCID: PMC8483580, https://doi.org/10.1088/1361-6560/ac15a5
  • Bertolet A, Cortés-Giraldo MA, Carabe-Fernandez A. Implementation of the microdosimetric kinetic model using analytical microdosimetry in a treatment planning system for proton therapy. Phys Med. 2021 Jan;81:69-76. PMID: 33440283, https://doi.org/10.1016/j.ejmp.2020.11.024
  • Bertolet A, Wals A, Miras H, Macías J. Organic generation of real-world real-time data for clinical evidence in radiation oncology. Int J Med Inform. 2020 Dec;144:104301. PMID: 33091831, https://doi.org/10.1016/j.ijmedinf.2020.104301
  • Bertolet A, Grilj V, Guardiola C, Harken AD, Cortés-Giraldo MA, Baratto-Roldán A, Carabe A. Experimental validation of an analytical microdosimetric model based on Geant4-DNA simulations by using a silicon-based microdosimeter. Radiat Phys Chem Oxf Engl 1993. 2020 Nov;176. PMID: 33100611, PMCID: PMC7583143, https://doi.org/10.1016/j.radphyschem.2020.109060
  • Bertolet A, Cortés-Giraldo MA, Carabe-Fernandez A. An Analytical Microdosimetric Model for Radioimmunotherapeutic Alpha Emitters. Radiat Res. 2020 Oct 2;194(4):403-410. PMID: 33045091, https://doi.org/10.1667/RADE-20-00045.1
  • Bertolet A, Carabe-Fernandez A. Clinical implications of variable relative biological effectiveness in proton therapy for prostate cancer. Acta Oncol. 2020 Oct;59(10):1171-1177. PMID: 32427011, https://doi.org/10.1080/0284186X.2020.1762928
  • Bertolet A, Carabe A. Modelling Dose Effects from Space Irradiations: Combination of High-LET and Low-LET Radiations with a Modified Microdosimetric Kinetic Model. Life (Basel). 2020 Aug 23;10(9). PMID: 32842519, PMCID: PMC7555955, https://doi.org/10.3390/life10090161
  • Bertolet A, Carabe A. Proton monoenergetic arc therapy (PMAT) to enhance LETd within the target. Phys Med Biol. 2020 Aug 19;65(16):165006. PMID: 32428896, https://doi.org/10.1088/1361-6560/ab9455
  • Carabe A, Karagounis IV, Huynh K, Bertolet A, François N, Kim MM, Maity A, Abel E, Dale R. Radiobiological effectiveness difference of proton arc beams versus conventional proton and photon beams. Phys Med Biol. 2020 Aug 31;65(16):165002. PMID: 32413889, https://doi.org/10.1088/1361-6560/ab9370
  • Bertolet A, Cortés-Giraldo MA, Souris K, Carabe A. A kernel-based algorithm for the spectral fluence of clinical proton beams to calculate dose-averaged LET and other dosimetric quantities of interest. Med Phys. 2020 Jun;47(6):2495-2505. PMID: 32124463, https://doi.org/10.1002/mp.14108
  • Bertolet A, Cortés-Giraldo MA, Carabe-Fernandez A. On the concepts of dose-mean lineal energy, unrestricted and restricted dose-averaged LET in proton therapy. Phys Med Biol. 2020 Apr 2;65(7):075011. PMID: 32023557, https://doi.org/10.1088/1361-6560/ab730a
  • Carabe-Fernandez A, Bertolet-Reina A, Karagounis I, Huynh K, Dale RG. Is there a role for arcing techniques in proton therapy?. Br J Radiol. 2020 Mar 1;93(1107):20190469. PMID: 31860338, PMCID: PMC7066964, https://doi.org/10.1259/bjr.20190469
  • Bertolet A, Cortés-Giraldo MA, Souris K, Cohilis M, Carabe-Fernandez A. Calculation of clinical dose distributions in proton therapy from microdosimetry. Med Phys. 2019 Dec;46(12):5816-5823. PMID: 31603992, https://doi.org/10.1002/mp.13861
  • Bertolet A, Baratto-Roldán A, Cortés-Giraldo MA, Carabe-Fernandez A. Segment-averaged LET concept and analytical calculation from microdosimetric quantities in proton radiation therapy. Med Phys. 2019 Sep;46(9):4204-4214. PMID: 31228264, https://doi.org/10.1002/mp.13673
  • Bertolet A, Baratto-Roldán A, Barbieri S, Baiocco G, Carabe A, Cortés-Giraldo MA. Dose-averaged LET calculation for proton track segments using microdosimetric Monte Carlo simulations. Med Phys. 2019 Sep;46(9):4184-4192. PMID: 31169910, https://doi.org/10.1002/mp.13643
  • Miras H, Jiménez R, Perales Á, Terrón JA, Bertolet A, Ortiz A, Macías J. Monte Carlo verification of radiotherapy treatments with CloudMC. Radiat Oncol. 2018 Jun 27;13(1):99. PMID: 29945681, PMCID: PMC6020449, https://doi.org/10.1186/s13014-018-1051-9

Conference talks

  • Bertolet A. Computational modeling in radiopharmaceutical therapy. 5th Annual Targeted Radiopharmaceuticals Summit. Berlin, Germany, December 2023.
  • Bertolet A. Microdosimetry and DNA damage in radiopharmaceutical therapy. EURADOS Pilot Group Meeting on Dosimetry in Nuclear Medicine. Munich, Germany and virtual, October 2023.
  • Bertolet A. Path to Independence: How to secure your first grant as an early-stage investigator? / Invited Presentation. American Association of Physicists in Medicine, Houston, TX, July 2023.
  • Bertolet A. The physics behind proton boron capture therapy / Invited Presentation. American Association of Physicists in Medicine, Houston, TX, July 2023.
  • Bertolet A. Open-Source Data and Tools in Medical Physics / Invited Presentation. Global Research and Scientific Innovation Committee (GRSIC), AAPM and IOMP, Virtual, June 2023.
  • Bertolet A. RBE in proton therapy / Invited Presentation. Particle Therapy Cooperative Group, Madrid, Spain, June 2023.
  • Bertolet A, Paganetti H, Schuemann J. In-silico modeling of RBE for damage to the DNA as a function of microdosimetry for protons and alpha particles / Selected Oral Abstract. International Conference of Mini- Micro- Nano-Dosimetry, Noosa, Australia, February 2023.
  • Bertolet A. Challenges and opportunities in radiopharmaceutical therapy / Invited Presentation. Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia, February 2023.
  • Bertolet A. Monte Carlo simulations for radiation biology and dosimetry in radiopharmaceutical therapy / Invited Presentation. Oak Ridge National Lab, Oak Ridge, TN, November 2022.
  • Bertolet A, Paganetti H, Schuemann J. Integrating the production of radicals from water radiolysis into the framework of microdosimetry / Selected Oral Abstract. Particle Therapy Cooperative Group, Miami, FL, June 2022.
  • Bertolet A, Wehrenberg-Klee E, Bobić M, Paganetti H, Schuemann J. TOPAS for 90Y-microsphere radioembolization dosimetry. International Conference on Monte Carlo for Medical Applications / Selected Oral Abstract. Antwerp, Belgium, April 2022.
  • Bertolet A, Abolfath R, Carlson D, Lustig RA, Hill-Kayser C, Alonso-Basanta M, Carabe A. Dose-averaged LET in proton therapy for patients with MRI abnormalities and its role in normal tissue complication probability / Selected Oral Abstract. American Association of Physicists in Medicine, virtual. July 2021.
  • Bertolet A, Schuemann J, Ramos-Méndez J, Paganetti H. Microdosimetry of alpha particles correlates with induction of direct damage to DNA / Selected Oral Abstract. Particle Therapy Cooperative Group, virtual. June 2021.
  • Bertolet A, Carabe A, Cortés-Giraldo MA. Microdosimetry for proton radiotherapy / Selected Oral Abstract. III Conference RSEF/IFIMED on Medical Physics, virtual. December 2020.
  • Bertolet A, Miras H, Wals A, Macías J. Customizing MOSAIQ: Paperless workflow and real data in real-time / Selected Oral Abstract. I Virtual Conference of Spanish Young Medical Physicists (SEFM), November 2020.
  • Bertolet A. Microdosimetría y RBE en protonterapia / Selected Oral Abstract. I Conference of Spanish Young Medical Physicists (SEFM), November 2020.
  • Bertolet A, Carabe A. Analytical models for microdosimetry to calculate dose from alpha-emitters used in radioimmunotherapy / Selected Oral Abstract. Radiation Research Society Winter Workshop, Big Sky, MN, March 2020.
  • Bertolet A, Cortés-Giraldo MA, Carabe A. An analytical approach to model microdosimetric distributions in proton beams for LETd calculations / Selected Oral Abstract. Particle Therapy Cooperative Group, Manchester, UK, June 2019.
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