Carbon-ion radiotherapy for urological cancers

Abstract

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Keywords: carbon-ion radiotherapy; local control; prostate cancer; renal cell carcinoma; toxicity.

FIGURE 1

Carbon‐ion therapy institutes in Japan

FIGURE 2

A schema of treatment doses for X‐ray, proton, and carbon‐ion beams, where the proton and carbon‐ion beams are optimized to cover a tumor with SOBP. Reprinted from Figure 1 of a reference reported by Ishikawa et al. © 2019 The Authors

FIGURE 3

Microscopic spatial dose distributions pertaining to the irradiations delivering the same macroscopic dose of 1 Gy: 15 MeV/u stopping carbon ions with LET of 13 keV/μm (left), 270 MeV/u high‐energetic carbon ions with LET of 118 keV/μm (middle), and 100 keV electrons with a LET of 0.5 keV/μm (right). The diameter of the circle in each panel is 10 μm. Reprinted from Figure 2 of a reference reported by Krämer et al. © 2012 The Authors and IOP Publishing [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Physical (black) and clinical dose distribution (red) of therapeutic carbon‐ion beams for a tumor volume located at 94–154 mm depth. The uniform clinical dose of 5.8 Gy (RBE) was designed at the tumor volume [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Difference in dose distributions of CIRT for prostate cancer. Compared with using passive scattering beams (a), irradiated doses and volumes at the rectum and bone can be reduced using spot scanning beams (b). In the prospective study for ultra‐hypofractionated CIRT, the urethra doses are constrained using the inverse treatment planning method (c). The rectal dose can be also much reduced using a commercial rectal spacer (d) [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

Trends in the numbers of CIRT institutes and treated patients with prostate cancer

FIGURE 7

A representative RCC case after CIRT. Dose distribution of CIRT (a), and changes in a tumor on CT images at before (b) and 1 (c), 3 (d), and 10 (e) years after CIRT [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 8

A large retroperitoneal sarcoma (13.6 × 11.5 cm) of a 78‐year‐old male treated with CIRT at a total irradiation dose of 70.4 Gy (RBE) in 16 fractions (a). The red, pink, green, blue lines indicated 97, 70, 50, 30% of the total dose. The tumor located in the right pelvic retroperitoneum (b), and it has gradually shrunk and the tumor size was 7.5 × 5.9 cm at 2 years after CIRT (c) [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 9

Schematic perspective view of Quantum Scalpel [Colour figure can be viewed at wileyonlinelibrary.com]