AB014. Developments towards an adequate description of the dose-response relationship in the context of boron neutron capture therapy glioblastoma treatments
Abstract

AB014. Developments towards an adequate description of the dose-response relationship in the context of boron neutron capture therapy glioblastoma treatments

Barbara Marcaccio1,2,3, Agustina Portu2,3,4, Gustavo Santa Cruz2, Cinzia Ferrari5,6, Laura Cansolino5,6, Marco Crepaldi6, Daniele Dondi5,7, Ana Mailén Dattoli Viegas2,4, Dhanalakshmi Vadivel5,7, Ian Postuma5, Gisela Saint Martin2, Silvia I. Thorp2, Emiliano C. C. Pozzi2, Paula Curotto2, Silva Bortolussi1,5, Sara González2,3,4

1Department of Physics, University of Pavia, Pavia, Italy; 2Radiobiology and Physics Departments, National Atomic Energy Commission (CNEA), Buenos Aires, Argentina; 3National University of San Martín (UNSAM), Buenos Aires, Argentina; 4National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina; 5National Institute of Nuclear Physics (INFN), Unit of Pavia, Pavia, Italy; 6Department of Clinical and Surgical Sciences, Integrated Unit of Experimental Surgery, Advanced Microsurgery and Regenerative Medicine, University of Pavia, Pavia, Italy; 7Department of Chemistry, University of Pavia, Pavia, Italy

Correspondence to: Barbara Marcaccio, MD. Department of Physics, University of Pavia, Via Agostino Bassi, 6, 27100 Pavia, Italy; Radiobiology and Physics Departments, National Atomic Energy Commission (CNEA), Buenos Aires, Argentina; National University of San Martín (UNSAM), Buenos Aires, Argentina. Email: barbara.marcaccio01@universitadipavia.it.

Background: Glioblastoma multiforme (GBM) is a brain tumor that stands out for its malignancy, rapid progression, and resistance to conventional treatments: irradiation and chemotherapy after surgery. Despite improvements in diagnostic modalities, the survival time remains less than 1 year. In this context, boron neutron capture therapy (BNCT) is particularly interesting. It is a biologically cell-directed type of radiotherapy, and its application exerts deleterious effects on tumor cells and not on the surrounding healthy tissue, improving local tumor control and patient survival. The total BNCT absorbed dose results from a mixed field of radiation with different biological effectiveness. The complexity of this field makes it difficult to predict the therapeutic effect for a given total absorbed dose. Therefore, it is necessary to translate the BNCT dose into a dose delivered with conventional photon radiotherapy, for which the dose-effect relationship is known. This study aims to establish a photon isoeffective dose model for GBM based on a radiobiological experiment.

Methods: Cell survival curves were constructed as a function of absorbed dose using the human glioblastoma cell line U87. Monolayer cultures were irradiated with a Co-60 photon source and thermal neutrons at the University of Pavia (Italy). The study involving the human glioblastoma cell line U87 was conducted in accordance with ethical standards. Commercial cell lines purchased by Merck KGaA, Darmstadt, Germany, complied with relevant ethical guidelines for research use. The radiobiological parameters of these curves and those derived from a rat gliosarcoma model were determined and used to feed the photon isoeffective dose model. The dosimetry of a GBM patient case was analyzed. Comparisons of the results obtained with both sets of radiobiological parameters were performed. A boron distribution analysis at the cellular level was also initiated as part of this work. Experiments of neutron autoradiography comprising cells were carried out in Argentina using the thermal column of the RA-3 reactor of Buenos Aires.

Results: The retrospective study of the GBM clinical case revealed a 29% difference between the tumor dose-volume histograms obtained for the two sets of radiobiological parameters, with the doses based on U87 cell survival experiments being lower than those for the gliosarcoma model used in the BNCT clinical trial to obtain relative biological effectiveness factors.

Conclusions: The results show the importance of conducting appropriate preclinical experiments and the need to feed the model to express the dose in photon units with the correct radiobiological parameters.

Keywords: Boron neutron capture therapy (BNCT); glioblastoma multiforme (GBM); dosimetry; neutron autoradiography

Acknowledgments

The authors acknowledge the RA-3 staff for irradiating the samples in the thermal column of the Ezeiza reactor.

Footnote

Funding: This work was supported by the National Institute for Nuclear Physics (INFN, CSN5), project IT_STARTS, the National Agency for Promotion of Science and Technology (ANPCyT) of Argentina (No. 2019-01047), and Universidad Nacional de San Martin, Buenos Aires, Argentina.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab014/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Cell lines used are immortalized and commercially available. No primary cell lines derived from patients were used. Images of the representative patient were obtained from a public database called The Cancer Imaging Archive (TCIA), and no ethical issues are involved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/tro-25-ab014
Cite this abstract as: Marcaccio B, Portu A, Cruz GS, Ferrari C, Cansolino L, Crepaldi M, Dondi D, Dattoli Viegas AM, Vadivel D, Postuma I, Saint Martin G, Thorp SI, Pozzi ECC, Curotto P, Bortolussi S, González S. AB014. Developments towards an adequate description of the dose-response relationship in the context of boron neutron capture therapy glioblastoma treatments. Ther Radiol Oncol 2025;9:AB014.

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