National Effort to Re-Establish Heavy Ion Cancer Therapy in the United States

Abstract

In this review, we attempt to make a case for the establishment of a limited number of heavy ion cancer research and treatment facilities in the United States. Based on the basic physics and biology research, conducted largely in Japan and Germany, and early phase clinical trials involving a relatively small number of patients, we believe that heavy ions have a considerably greater potential to enhance the therapeutic ratio for many cancer types compared to conventional X-ray and proton radiotherapy. Moreover, with ongoing technological developments and with research in physical, biological, immunological, and clinical aspects, it is quite plausible that cost effectiveness of radiotherapy with heavier ions can be substantially improved.

The rationale for a carbon ion radiation therapy facility in Australia

“…Early radiation therapy with heavier ions Radiation therapy using He ions began in the late1950s and with heavier ions in the 1970s, at the Lawrence Berkeley National Accelerator Laboratory (LBNL), Berkeley, CA, USA. [33][34][35][36] Their use was not only based on dose distribution advantages, but also expectations that heavier ions had radiobiological properties that could improve tumour control for difficult-to-treat cancers. The LBNL accelerator was de-commissioned in 1992.…”

“…CIRT was used between 1977 and 1992. [33][34][35][36] (Note: these ions are described as 'heavier' relative to protons, but ions with Z of 1-10 are also 'light ions' relative to even heavier ions in nuclear and particle physics, so both terminologies are used). 37…”

“…27,56 Additionally, they have a potential benefit from hypofractionation, that is, shorter course, higher dose-per-fraction treatments. RBE drops as dose/ fraction increases, but by significantly more for typical normal tissues than for tumours, so hypofractionation of CIRT can improve the therapeutic ratio, 27,36,50,61 with many clinical studies taking this approach. 62 This also reduces the attendances required per patient and increases facility throughput.…”

“…62 This also reduces the attendances required per patient and increases facility throughput. Additional radiobiology-based advantages reported 27,36,50,56 include reduced dependence on the cell cycle phase, 50 reduced angiogenesis, 63 enhanced apoptosis in radioresistant cancer stem cells (CSCs) 50,64 and exploitable synergistic effects when CIRT is used in combination with targeted therapy 50,65 or in combination with immunotherapy. 43,50,51,66,67 Further details of CIB radiobiology, at both molecular and classical (RBE, OER) levels, are discussed in references, [50][51][52][53] including biological effects, mechanisms for DNA damage and repair and for cell and tumour responses.…”

“…37 However, this uncertainty requires care in comparing clinical doses and outcomes between centres and clinical trials and in transferring experience between the different systems. 31,36,37,56,79,82 Summary of why CIRT is the second main PT modality Together, the physical and biological effect characteristics provide significant potential advantages for tumour control from heavier ions, especially for radioresistant (to XRT and PBT) tumours, including hypoxic tumours, and those with a high number of CSCs. 27,36,50,62 This depends on conformality, higher RBE, lower OER and the potential from hypofractionation.…”