Bringing the heavy: carbon ion therapy in the radiobiological and clinical context

Abstract

Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/β ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.

Treatment Planning Studies in Patient Data With Scanned Carbon Ion Beams for Catheter‐Free Ablation of Atrial Fibrillation

“…This is mostly due to high costs of 12 C facilities, which require a stronger accelerator than H + facilities. 10,13,14 Recently, the NIH provided a federal planning grant to UT Southwestern (Dallas, TX) and the UCSF Medical Center (San Francisco, CA) for development of the first 12 C facilities in the US. 15 This will help in determining cost-effectiveness of 12 C particle therapy centers in treatment of several different malignant tumors.…”

“…10 Currently 8 facilities, located in Japan, China, Italy, and Germany, provide 12 C therapy. These so far have treated over 15,000 patients.…”

Clustered double-strand breaks in heterochromatin perturb DNA repair after high linear energy transfer irradiation

“…Charged-particle radiotherapy with carbon ions is an emerging technique, especially for tumours that are radioresistant or located close to critical organs [1]. The unique energy deposition pattern of carbon ions, with highly concentrated energy deposited in the socalled ''Bragg peak", can substantially improve the dose distribution and therapeutic efficacy compared with those of conventional photon-based radiotherapy.…”

Clinical Evidence and Radiobiological Background of Particle Radiation Therapy

“…Striking biological effects are, e.g. a reduced cell repair capacity and a decreased dependency on the cell cycle as compared to photon radiation [ 9 ]. Further putative advantages have been discovered just recently: carbon ion radiation suppresses metastasis and angiogenesis [ 10 ] and is discussed to trigger an immune response [ 11 ].…”