Proton (p) and carbon (C) ion beams are in clinical use for cancer treatment, although other particles such as He, Be, and B ions have more recently gained attention. Identification of the most optimal ion beam for radiotherapy is a challenging task involving, among others, radiobiological characterization of a beam, which is depth-, energy-, and cell type- dependent. This study uses the FLUKA and MCDS Monte Carlo codes in order to estimate the relative biological effectiveness (RBE) for several ions of potential clinical interest such as p, 4He, 7Li, 10Be, 10B, and 12C forming a spread-out Bragg peak (SOBP). More specifically, an energy spectrum of the projectiles corresponding to a 5-cm SOBP at a depth of 8 cm was used. All secondary particles produced by the projectiles were considered and RBE was determined based on radiation-induced Double Strand Breaks (DSBs), as calculated by MCDS. In an attempt to identify the most optimal ion beam, using the latter data, biological optimization was performed and the obtained depth–dose distributions were inter-compared. The results showed that 12C ions are more effective inside the SOBP region, which comes at the expense of higher dose values at the tail (i.e., after the SOBP). In contrast, p beams exhibit a higher D S O P B / D E n t r a n c e ratio, if physical doses are considered. By performing a biological optimization in order to obtain a homogeneous biological dose (i.e., dose × RBE) in the SOBP, the corresponding advantages of p and 12C ions are moderated. 7Li ions conveniently combine a considerably lower dose tail and a D S O P B / D E n t r a n c e ratio similar to 12C. This work contributes towards identification of the most optimal ion beam for cancer therapy. The overall results of this work suggest that 7Li ions are of potential interest, although more studies are needed to demonstrate the relevant advantages. Future work will focus on studying more complex beam configurations. [ABSTRACT FROM AUTHOR]