Biology contribution
Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center

Presented at the ASTRO 43rd Annual Meeting in San Francisco, CA, November 4–8, 2001.
https://doi.org/10.1016/S0360-3016(02)02949-8Get rights and content

Abstract

Purpose: To assess the biologic effects of proton and carbon ion beams before clinical use.

Methods and Materials: Cultured cells from human salivary gland cancer (HSG cells) were irradiated at 5 points along a 190 MeV per nucleon proton and a 320 MeV per nucleon carbon ion beam, with Bragg peaks modulated to 6 cm widths. A linac 4 MV X-ray was used as a reference. Relative biologic effectiveness (RBE) values at each point were calculated from survival curves. Cells were also irradiated in a cell-stack phantom to identify that localized cell deaths were observed at predefined depth. Total body irradiation of C3H/He mice was performed, and the number of regenerating crypts per jejunal section was compared to calculate intestinal RBE values. For carbon ion and referential 4 MV X-ray beams, mouse right legs were irradiated by four-fractional treatment and followed up for skin reaction scoring.

Results: RBE values calculated from cell survival curves at the dose that would reduce cell survival to 10% (D10) ranged from 1.01 to 1.05 for protons and from 1.23 to 2.56 for carbon ions. The cell-stack phantom irradiation revealed localized cell deaths at predefined depth. The intestinal RBE values ranged from 1.01 to 1.08 for protons and from 1.15 to 1.88 for carbon ions. The skin RBE value was 2.16 at C320/6 cm spread-out Bragg peak (SOBP) center.

Conclusion: The radiobiologic measurements of proton and carbon ion beams at Hyogo Ion Beam Medical Center are consistent with previous reports using proton beams in clinical settings and carbon ion beams with similar linear energy transfer (LET) values.

Introduction

Cancer death has become one of the biggest concerns in even the health administration department of a local government in Japan. Hyogo prefecture government organized the Hyogo Strategy Committee for Cancer Control in 1987 because of the increasing cancer death cases. In 1992, the committee proposed ion beam cancer therapy as a promising treatment modality to promote in the future because of its excellent local effects and minimal damage to surrounding normal tissues. The governor of Hyogo adopted the proposal and ordered further research to create an ion beam treatment facility under prefectural management.

Based on thorough research, a hospital specializing in ion beam cancer therapy was established by the Hyogo prefecture government. The hospital, named the Hyogo Ion Beam Medical Center (HIBMC), commenced the first patient treatment in May 2001.

HIBMC has a dedicated clinical synchrotron with a diameter of 30 meters that can accelerate protons up to 230 MeV per nucleon (30 cm range in water) and carbon ions up to 320 MeV per nucleon (20 cm range in water). Proton and carbon ion beams can form Bragg peaks at arbitrary depths by changing accelerating energies and degrader thickness. At present, spread-out Bragg peak (SOBP) beams are used for patient treatment at HIBMC. Bragg peaks are modulated to fit the width of the planning target volume (PTV) by passing through various kinds of bar ridge filters. Bar ridge filters are designed to obtain uniform physical doses in SOBP portions for protons (1) and uniform biologic doses for carbon ions (2).

Before starting patient treatment, intensive preclinical assessment was performed in both physical and biologic aspects. Three-dimensional measurements by a columnar water phantom demonstrated that both proton and carbon ion SOBP beams can give prescribed physical doses to predefined depths within the accuracy of ±2.5%.

SOBP beams of protons and carbon ions are known to have various values of relative biological effectiveness (RBE) at different depths 3, 4. We performed biologic experiments on our SOBP beams for two obvious purposes. The first is to confirm the uniformity of biologic doses in PTV positions even considering various RBE values. The second is to estimate biologic RBE (bRBE) values using several biologic systems and finally decide clinical RBE (cRBE) values to apply to patient treatment at our facility. As clearly described by Wambersie (5), although biologic RBE is a useful concept to understand radiation qualities, its value is always associated with experimental uncertainties and cannot directly be applied to patient treatment. This is what happened in starting carbon ion therapy at the National Institute of Radiological Sciences (NIRS) in Chiba, Japan (6). The final decision of the RBE values adopted in clinical settings (i.e., clinical RBE values) should be made by radiation oncologists on the basis of available radiobiological data on their responsibility. Following this rationale, we determined clinical RBE values of proton and carbon ion beams at HIBMC before clinical use based on radiobiological experiments.

In this study, we report initial results of the preclinical biologic assessment of proton and carbon ion beams at HIBMC and describe basic biologic concepts for our ion beam cancer therapy.

Section snippets

Ion beams and referential photon beam

The beam energies of protons are currently fixed to three steps (150 MeV, 190 MeV, 230 MeV) at HIBMC, and the corresponding water ranges of monoenergetic beams are 15 cm, 23 cm, and 33 cm, respectively. Likewise the carbon ion energies are fixed to two steps (250 MeV and 320 MeV), and the corresponding water ranges of monoenergetic beams are 12 cm and 19 cm. Based on statistical analyses of clinical data of the preceding ion beam treatment facilities in Japan (NIRS and Tsukuba University) 7, 8,

Survival curves of HSG cells

Figure 2a shows irradiation points of HSG cells along P190/6 cm SOBP. Cell survival curves of X4 and P190/6 cm SOBP are summarized in Fig. 2b. Six survival curves are almost identical. Cell RBE values at a D10 dose level (cell RBE10) ranged from 1.01 to 1.05. The average and 1 SD of cell RBE10 values obtained from three independent experiments were 1.03 (±0.042) at 5 mm, 1.01 (±0.019) at 168 mm, 1.02 (±0.058) at 190 mm, 1.05 (±0.016) at 212 mm, and 1.05 (±0.028) at 216 mm depth in water. The

Discussion

At present, NIRS is the only facility to treat patients with carbon ion SOBP beams. Several kinds of cultured cells (HSG, T1, V79, etc.) were used in preclinical radiobiological experiments at NIRS. The final design of bar ridge filters for carbon ions was decided to best flatten biologic doses in SOBP portions at a D10 dose level of HSG cell survivals (6). Because HIBMC is the second facility to start cancer therapy with carbon ion SOBP beams and has adopted a common code to design carbon ion

References (16)

There are more references available in the full text version of this article.

Cited by (128)

  • First-In-Human Phase 1 Study of a Nonwoven Fabric Bioabsorbable Spacer for Particle Therapy: Space-Making Particle Therapy (SMPT)

    2019, Advances in Radiation Oncology
    Citation Excerpt :

    The planning target volume (PTV) was defined as the CTV plus a setup margin (5 mm) and an internal margin (1 mm) under the respiratory gating system.18 The relative biological effectiveness (RBE) values for protons and carbon ions at HIBMC are 1.1 and 2 to 3.7, respectively, depending on the depth in the spread-out Bragg peak.19 The dose constraints in the 32-fraction protocol for the small bowel, large bowel, and rectum were a maximum dose (Dmax) of ≤53 Gy (RBE), Dmax of ≤59 Gy (RBE), and volume receiving ≥65 Gy (RBE) (V65) of ≤17% and V40 of ≤35%, respectively.

View all citing articles on Scopus

This work was supported in part by Grant-in-aid for Cancer Research No. 11-6 from the Ministry of Health, Labor and Welfare, Japan.

View full text