BIANCA, a biophysical model of cell survival and chromosome damage by protons, C-ions and He-ions at energies and doses used in hadrontherapy
Open accessAbstract
An upgraded version of the BIANCA II biophysical model, which describes more realistically interphase chromosome organization and the link between chromosome aberrations and cell death, was applied to V79 and AG01522 cells exposed to protons, C-ions and He-ions over a wide LET interval (0.6–502 keV µ m −1 ), as well as proton-irradiated U87 cells. The model assumes that (i) ionizing radiation induces DNA ‘cluster lesions’ (CLs), where by definition each CL produces two independent chromosome fragments; (ii) fragment (distance-dependent) mis-rejoining, or un-rejoining, produces chromosome aberrations; (iii) some aberrations lead to cell death. The CL yield, which mainly depends on radiation quality but is also modulated by the target cell, is an adjustable parameter. The fragment un-rejoining probability, f , is the second, and last, parameter. The value of f , which is assumed to depend on the cell type but not on radiation quality, was taken from previous studies, and only the CL yield was adjusted in the present work. Good agreement between simulations and experimental data was obtained, suggesting that BIANCA II is suitable for calculating the biological effectiveness of hadrontherapy beams. For both V79 and AG01522 cells, the mean number of CLs per micrometer was found to increase with LET in a linear-quadratic fashion before the over-killing region, where a less rapid increase, with a tendency to saturation, was observed. Although the over-killing region deserves further investigation, the possibility of fitting the CL yields is an important feature for hadrontherapy, because it allows performing predictions also at LET values where experimental data are not available. Finally, an approach was proposed to predict the ion-response of the cell line(s) of interest from the ion-response of a reference cell line and the photon response of both. A pilot study on proton-irradiated AG01522 and U87 cells, taking V79 cells as a reference, showed encouraging results.
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“For example, Cornforth and Bedford observed correspondence between fibroblast cell death and asymmetrical chromosome aberrations (2), and Ballarini and Carante implemented this idea in the BIANCA biophysical model to predict the biological effectiveness of different hadrontherapy beams (3, 4).”
BackgroundA Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits
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“Since, in space research, a major uncertainty is related to the RBE of space radiation [21], in this work, we applied the BIANCA biophysical model [22,23] to calculate the RBE of galactic cosmic rays for the induction of both chromosome aberrations, which are indicators of cancer risk [24–29], and cell death, which is…”
Self-citationPfuhl, T., Friedrich, T., & Scholz, M. (2021) · Medical Physics · doi:10.1002/mp.15343 · Cited by 29 · see citing works
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“…the giant loop binary lesionmodel (GLOBE, Friedrich et al 2012), the biophysical analysis of cell death and chromosome aberrationsmodel (BIANCA,Carante et al 2018), nanodosimetric models (Villegas et al 2016, Conte et al 2018, Schneider et al 2020), themulti scale approach (MSA, Surdutovich…”
BackgroundIn vivo validation of the BIANCA biophysical model: benchmarking against rat spinal cord RBE data
Carante, M. P., Aricò, G., Ferrari, A., Karger, C. P., Kozlowska, W., Mairani, A., Sala, P., & Ballarini, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113973 · Cited by 21 · see citing works
“, [16,27,35], the main input information for running a simulation with BIANCA consist of the radiation type (photons, light ions or heavy ions), the yield of CLs and the f value, the shape of the cell nucleus (that can be either spherical or cylindrical) and its size, as well as the treatment parameters LET and absorb…”
BackgroundMethodSelf-citationTechnological Developments and Future Perspectives in Particle Therapy: A Topical Review
Kraan, A. C., & Guerra, A. D. (2024) · IEEE Transactions on Radiation and Plasma Medical Sciences · doi:10.1109/trpms.2024.3372189 · Cited by 19 · see citing works
“Another recent development in the coupling of radio-biological models with general purpose MC regards the BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA) model [119].”
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“Since analogous predictions have been obtained in a previous work for AG01522 human fibroblasts exposed to proton beams [11], in the present work the comparison with AG01522 data was extended to different C-ion beams (with LET of 48.”
Self-citationCarante, M. P., Embriaco, A., Aricò, G., Ferrari, A., Mairani, A., Mein, S., Ramos, R., Sala, P., & Ballarini, F. (2021) · Physics in Medicine & Biology · doi:10.1088/1361-6560/ac25d4 · Cited by 15 · see citing works
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Ganjeh, Z. A., Eslami-Kalantari, M., Loushab, M. E., & Mowlavi, A. A. (2020) · Radiation Physics and Chemistry · doi:10.1016/j.radphyschem.2020.109249 · Cited by 14 · see citing works
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Self-citationFirst application of the BIANCA biophysical model to carbon-ion patient cases
Kozłowska, W., Carante, M. P., Aricò, G., Embriaco, A., FERRARI, A., Magro, G., Mairani, A., Ramos, R. L., SALA, P. R., Georg, D., et al. (2022) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ac702b · Cited by 12 · see citing works
Self-citationKalospyros, S. A., Nikitaki, Z., Kyriakou, I., Kokkoris, M., Emfietzoglou, D., & Georgakilas, A. G. (2021) · Molecules · doi:10.3390/molecules26040840 · Cited by 12 · see citing works
“The mechanistic model BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) in addition to cell survival curves predicts chromosome aberrations, in the form of chromosome aberration dose-response curves which are considered as an important indicator of tissue damage [37,38].”
BackgroundParisi, A., Furutani, K. M., & Beltran, C. J. (2025) · Medical Physics · doi:10.1002/mp.17755 · Cited by 10 · see citing works
Ramos, R. L., Carante, M. P., Bernardini, E., FERRARI, A., SALA, P. R., Vercesi, V. I., & Ballarini, F. (2024) · Life Sciences in Space Research · doi:10.1016/j.lssr.2024.03.006 · Cited by 10 · see citing works
“First, such work has been performed for ions with Z between 1 (protons) and 8 (Oxygen) (Carante et al., 2018; Carante et al., 2019), thus allowing for applications in the field of cancer hadrontherapy (Carante et al., 2019; Carante et al., 2020; Carante et al., 2021; Embriaco et al., 2021;…”
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“BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) [16,55,56] is a biophysical model allowing to compute cell survival probabilities as well as chromosome aberration doseresponse curves for different types of irradiation.”
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“…and Paganetti 2016), different approaches (i.e. Kellerer andRossi 1978,Hawkins 1994, Scholz andKraft 1994, Kanai et al 1997, Kase et al 2006, Carlson et al 2008, Sato and Furusawa 2012, Carante et al 2018)were developed in parallel tomore-directly assess the biological endpoints of interest.”
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Fornalski, K. W., Adamowski, Ł., Bugała, E., Jarmakiewicz, R., Kirejczyk, M., Kopyciński, J., Krasowska, J., Kukulski, P., Piotrowski, Ł., Ponikowska, J., et al. (2022) · Dose-Response · doi:10.1177/15593258221138506 · Cited by 7 · see citing works
Ramos, R. L., Bernardini, E., Carante, M. P., FERRARI, A., SALA, P. R., Vercesi, V. I., & Ballarini, F. (2024) · Journal of Radiological Protection · doi:10.1088/1361-6498/ad7ff6 · Cited by 5 · see citing works
“In a previous work [14] we have proposed a different approach, based on cell-survival RBE values calculated by means of the BIANCA biophysical model developed by our research group e.g. [15, 16].”
Self-citationPREDICTING BIOLOGICAL EFFECTS ALONG HADRONTHERAPY DOSE PROFILES BY THE BIANCA BIOPHYSICAL MODEL
Carante, M. P., Cajiao, J. J. T., & Ballarini, F. (2018) · Radiation Protection Dosimetry · doi:10.1093/rpd/ncy263 · Cited by 5 · see citing works
Self-citationRamos, R. L., Embriaco, A., Carante, M. P., FERRARI, A., SALA, P. R., Vercesi, V. I., & Ballarini, A. F. (2022) · EPJ Web of Conferences · doi:10.1051/epjconf/202226103001 · Cited by 5 · see citing works
“In previous works [15,18,19], an approach has been developed to predict cell survival following ion irradiation of an arbitrary cell line for which the photon doseresponse is known, starting from a reference cell line; V79 cells have been chosen as a reference.”
BackgroundMethodSelf-citationCasali, A., Ramos, R. L., Ballarini, F., & Carante, M. P. (2024) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad98e1 · Cited by 3 · see citing works
“More details can be found in previous works (Ballarini and Carante 2016, Carante et al 2018, Ramos et al 2022).”
Self-citationPoignant, F., Pariset, E., Plante, I., Ponomarev, A. L., Evain, T., Viger, L., Slaba, T. C., Blattnig, S. R., & Costes, S. V. (2024) · Integrative Biology · doi:10.1093/intbio/zyae015 · Cited by 3 · see citing works
Formation of spread-out Bragg peak for helium-ion beam using microdosimetric kinetic model
Akagi, T., Maeda, T., Suga, M., & Yamashita, T. (2023) · Physica Medica · doi:10.1016/j.ejmp.2023.102587 · Cited by 3 · see citing works
Canay, E. I., Carante, M. P., Casali, A., Bernardini, E., Dondi, D., Vadivel, D., Cansolino, L., Delgrosso, E., Ferrari, C., Pullia, M. G., et al. (2025) · Life Sciences in Space Research · doi:10.1016/j.lssr.2025.09.002 · Cited by 2 · see citing works
Self-citationPoignant, F., Huff, J. L., Kunkel, S. R., Plante, I., & Slaba, T. C. (2025) · Life Sciences in Space Research · doi:10.1016/j.lssr.2025.04.009 · Cited by 2 · see citing works
Carante, M. P., Madonnini, A., Casali, A., Canay, E. I., Ramos, R. L., & Ballarini, F. (2026) · Biomedicines · doi:10.3390/biomedicines14030542 · Cited by 1 · see citing works
“The CL yield (mean number of CLs per Gy and per cell) and the chromosome fragment un-rejoining probability are the only two adjustable parameters; a detailed discussion on the model assumptions, as well as a description of the main simulation steps, can be found elsewhere [25].”
Self-citationCasali, A., Ramos, R. L., Ballarini, F., & Carante, M. P. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4815608
Self-citationComparison of in vitro cell survival predictions using Monte Carlo methods for proton irradiation
Buvinic, L., Galvez, S., Valenzuela, M. P., Sebastian, S., & Russomando, A. (2024) · Physica Medica · doi:10.1016/j.ejmp.2024.104867
Toumia, Y., Pullia, M. G., Charalampopoulou, A., Vitaliti, A., Domenici, F., Ferrarini, M., Facoetti, A., & Paradossi, G. (2025) · ACS Omega · doi:10.1021/acsomega.5c01785
Calculation of Doses and Biological Damage for Astronauts Exposed to Space Radiation
Ramos, R. L., Carante, M. P., Bernardini, E., Canay, E. I., Casali, A., Vercesi, V. I., & Ballarini, F. (2025) · IEEE International Workshop on Metrology for AeroSpace (MetroAeroSpace) · doi:10.1109/metroaerospace64938.2025.11114547
Self-citationTang, N. (2019) · doi:10.70675/5c028ef5z5b10z4510z9c39z4ef8f75b4449 · Cited by 1 · see citing works
Bernardini, E., Carante, M. P., Casali, A., Canay, E. I., Vercesi, V. I., Ballarini, F., & Ramos, R. L. (2026) · Health and Technology · doi:10.1007/s12553-026-01072-z
Self-citationThe photon isoeffective dose model for proton therapy
Valeriano, M. L., Ramos, R. L., Casali, A., Carante, M. P., Ballarini, F., Bortolussi, S., Cruz, G. A. S., & González, S. J. (2026) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ae788d
Self-citationCasali, A., Madonnini, A., Ramos, R. L., Canay, E. I., Ballarini, F., & Carante, M. P. (2026) · The European Physical Journal Special Topics · doi:10.1140/epjs/s11734-026-02396-7
Self-citationXiao, N., Cao, T., Liu, T., & Dai, Z. (2026) · Zeitschrift für Medizinische Physik · doi:10.1016/j.zemedi.2026.07.001
Liu, G. (2026) · The FASEB Journal · doi:10.1096/fj.202505071rrr
“Instead, more research is needed to further understand the effects of low-dose radiation” [19].”
Parisi, A., Furutani, K. M., Hartzell, S., 谭骏, Lu, B., Park, J. C., Yaddanapudi, S., Liang, X., & Beltran, C. J. (2026) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2026.08.046
- Authors
- Carante, M. P., Aimè, C., Cajiao, J. J. T., & Ballarini, F.
- Affiliations
- University of Pavia (IT)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Corresponding author
- Ballarini, Francesca
- Venue
- Physics in Medicine & Biology
- Publisher
- IOP Publishing
- Published
- 2018-03-26
- Volume
- 63
- Issue
- 7
- Pages
- 075007
- ISSN
- 0031-9155 (ISSN-L)
- 1361-6560
- OpenAlex
- W2790484694
- Cited by
- 52
- References
- 49
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 3
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Physics in Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nuclear Physics
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Keywords
- particle therapy, carbon ion radiotherapy, helium ion therapy, proton therapy, chromosomal abnormalities, cell survival, linear-quadratic model, LET dependence, biological effectiveness, V79 cells, U87 cells
- MeSH terms
- Animals, Cell Survival, Cells, Cultured, Chromosome Aberrations, Cricetulus, Dose-Response Relationship, Radiation, Fibroblasts, Glioma, Cricetinae, Helium, Humans, Models, Biological, Pilot Projects, Radiation, Ionizing, Proton Therapy, Heavy Ion Radiotherapy
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