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Scientific result | Cancer | Health ＆ life sciences
Evaluating the biological impact of hadrontherapy in healthy tissue upstream of a tumor is essential to assess the risk of radiation-induced sequelae. In the treatment of bone tumors, healthy articular cartilages are present in the path of the carbon ion beams. The development of 3D models has enabled IRCM's LARIA Research Team, in collaboration with IRAMIS and IBITECS (SBIGeM), to have relevant evaluation systems for these tissues.
Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis.
Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed.
As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model.
The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients.Read the French version.
Comparable senescence induction in 3D human cartilage model by exposure to therapeutic of X-rays or C-ions.(2016) Hamdi DH, Chevalier F, Groetz JE, Durantel F, Thuret JY, Mann C, Saintigny Y, Int. Journal of Radiation Oncology, biology. Special issue "Particle Therapy" In press, http://dx.doi.org/10.1016/j.ijrobp.2016.02.014
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