Recent advances in light ion radiation therapy

The fast development of energy- and intensity-modulated radiation therapy during the last two decades using photon and electron beams has when implemented resulted in a considerable improvement of radiation therapy, particularly if combined with radiobiologically based treatment optimization techniques. This has made intensity-modulated electron and photon beams as powerful as today's uniform dose proton therapy. To be able to cure also the most advanced hypoxic and radiation-resistant tumors of complex local spread, intensity-modulated light ion beams are really the ultimate tool and in clinical practice 2 to 3 times less expensive per patient treated than proton therapy. This development and the recent development of advanced tumor diagnostics based on PET-CT imaging of the tumor cell density open the field for new powerful radiobiologically based treatment optimization methods. The ultimate step is to use the unique radiobiologic and dose distributional advantages of light ion beams for truly optimized bioeffect planning where the integral three-dimensional dose delivery and tumor cell survival can be monitored by PET-CT imaging and corrected by biologically based adaptive therapy optimization methods. The main purpose of the present paper is to discuss the principal areas of development of therapy optimization, by considering the therapy chain from tumor diagnostics and the use of three-dimensional predictive assay to biologically based treatment optimization with special focus on the rapid clinical development of advanced light ion therapy. Besides the “classical” approaches using low ionization density hydrogen ions (protons, but also possibly deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be discussed. In the first one, lithium or beryllium or boron ions, which induce the least detrimental biologic effect to normal tissues for a given biologic effect in a small volume of the tumor, will be key particles. In the second approach, referred patients will be given a high-dose, high-precision “boost” treatment with carbon or oxygen ions during 1 week preceding the final treatment with conventional radiation in the referring hospital. The rationale behind these approaches is to minimize the high ionization density dose to the normal-tissue stroma outside but sometimes also inside the tumor bed and to ensure a more uniform and optimal biologic effectiveness in the tumor, also on the microscopic scale. The pres