The Current Status and Future Directions of Heavy Charged Particle Therapy in Medicine

摘要

As aggressive, 3D-conformal treatment has become the clearly accepted goal of radiation oncology, heavycharged-particle treatment with protons and heavier ions has concurrently and relentlessly ascended to the forefront. Protonsand helium nuclei, with relatively low linear-energy-transfer (LET) properties, have consistently been demonstrated to bebeneficial for aggressive (high-dose) local treatment of many types of tumors. Protons have been applied to the majority ofsolid tumors, and have reached a high degree of general acceptance in radiation oncology after three decades and 55,000patients treated. However, some 15% to 20% of tumor types have proven resistant to even the most aggressive low-LETirradiation. For these radio-resistant tumors, treatment with heavier ions (e.g., carbon) offers great potential benefit. Thesehigh-LET particles have increased relative biological effectiveness (RBE) that reaches its maximum in the Bragg peak.Irradiation with these heavier ions offers the unique combination of excellent 3D-dose distribution and increased RBE. Weare presently witnessing several, important parallel developments in particle therapy. Protons will likely continue theirexponential growth phase, and more compact design systems will make protons available to a larger patient population –thus becoming the "heavy charged particle of choice" for Cancer Centers with limited financial resources. In parallel, majoracademic efforts will further advance the field of heavier ion therapy, exploring all opportunities for particle treatment andcontinuing the search for the ideal particle(s) for specific tumors. The future of ion therapy will be best realized by clinicaltrials that have ready access to top-quality delivery of both protons and heavier ions that can be accurately shaped fortreatment of a specific pathology, and which will permit direct randomized-trial comparison of the effectiveness of thevarious ions for different diseases. Optimal results will require: (1) sophisticated target delineation that integrates CT, MRIand PET imaging; (2) reliable RBE modeling algorithms; (3) efficient beam-scanning technology that compensates fororgan movements; (4) online beam control proximal to and within the patient; and (5) better understanding of dose-fractionation parameters. The current status and the anticipated future directions of the role of particle therapy in medicine isa complex subject that involves a very intimate interplay of radiobiology, accelerator physics and radiation oncology. Theintention of this relatively brief manuscript is to describe the underlying principles, present the historical developments,highlight the clinical results, focus on the technical advances, and suggest likely future directions. We have also attempted topresent a balanced, consensus view of the past achievements and current strategies in particle therapy, in a manner ofinterest both to long-term experts and to educated newcomers to this field.