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In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS using HIMAC, which was then the world's only heavy ion accelerator complex dedicated to medical use in a hospital environment. Among several types of ion species, we have chosen carbon ions for cancer therapy because they had the most optimal properties in terms of possessing, both physically and biologically, the most effective dose-localization in the body. The purpose of the clinical study was to investigate the efficacy of carbon ion radiotherapy against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients had been entered into Phase I/II or Phase II studies and analyzed for toxicity and local tumor response. The results have shown that carbon ion radiotherapy has the potential ability to provide a sufficient dose to the tumor with acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors and those with histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the biological and physical properties of high-LET radiation, the efficacy of treatment regimens with small fractions in short treatment times has been confirmed for almost all types of tumors in carbon ion radiotherapy.

In June 1994, the world's first clinical center offering carbon ion radiotherapy opened at the National Institute of Radiological Science (NIRS), Japan. Among several types of ion species, carbon ions were chosen for cancer therapy because they were judged to have the most optimal properties in terms of superior physical and biological characteristics. As of March 2010, 5,196 patients have been registered for carbon ion radiotherapy. Clinical results have shown that carbon ion radiotherapy has the potential to provide a sufficient radiation dose to the tumor, while having acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors as well as histologically non-squamous cell tumor types such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the unique properties of carbon ions, treatment with small fractions within a short treatment period has been successfully carried out for a variety of tumors. This means that carbon ion radiotherapy can offer treatment for larger numbers of patients than is possible with other modalities over the same time period.

In carbon ion radiotherapy there is an urgent clinical need to develop objective tools for the conversion of relative biological effectiveness (RBE)-weighted doses based on different models. In this work we introduce a clinically oriented method to compare NIRS-based and LEM-based GyE systems, minimizing differences in physical dose distributions between treatment plans. Carbon ion plans were optimized on target volumes of cubic and spherical shapes, for RBE-weighted dose prescription levels ranging from 3.6 to 4.4 GyE. Plans were calculated for target sizes from 4 to 12 cm defining three beam geometries: single beam, opposed beam and orthogonal beam configurations. The two treatment planning systems currently employed in clinical practice were used, providing the NIRS-based and LEM-based GyE calculations. Physical dose distributions of NIRS-based and LEM-based treatment plans were compared. LEM-based prescription doses that minimize differences in physical dose distributions between the two systems were found. These doses were compared with the mean RBE-weighted dose obtained with a Monte Carlo code (FLUKA) interfaced with LEM I. In the investigated dose range, LEM-based RBE-weighted prescription doses, that minimize differences with NIRS plans, should be higher than NIRS reported prescription doses. The optimal dose depends on target size, shape and position, number of beams and dose level. The opposed beam configuration resulted in the smallest average prescription dose difference (0.45 ± 0.09 GyE). The second approach of recalculating NIRS RBE-weighted dose with a Monte Carlo code interfaced with LEM resulted in no significant difference with the results obtained from the planning study. The delivery of a voxel by voxel iso-effective plan, if different RBE models are employed, is not feasible; it is however possible to minimize differences in a treatment plan with the simple approach presented here. Dose prescription ultimately represents a clinical task under the responsibility of the radiation oncologist, the presented analysis intends to be a quantitative and objective way to assist the clinical decision.

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BackgroundOsteoradionecrosis (ORN) is a critical complication after carbon ion (C-ion) or photon radiotherapy (RT) for head and neck tumors. However, the risk factors for ORN after C-ion RT remain unclear. Therefore, the present study aimed to investigate the effects of the dose-volume relationship on and risk factors for ORN development after C-ion RT. We, however, focused on the maxillary bone because most tumors treated with C-ion RT were primarily located in the sinonasal cavity.MethodsThe patients enrolled in this study received more than 10% of the prescribed total dose of 57.6 Gy equivalent (GyE) in 16 fractions to their maxilla. All patients were followed up for more than 2 years after C-ion RT. Those with tumor invasion to the maxilla before C-ion RT or local recurrence after the treatment were excluded from the study to accurately evaluate the effects of irradiation on the bone. Sixty-three patients were finally selected. The severity of ORN was assessed according to the Common Terminology Criteria for Adverse Events version 4.0. The correlation between clinical and dosimetric parameters and ORN incidence was retrospectively analyzed.ResultsThe median follow-up period was 79 months. Of the 63 enrolled patients, 26 developed ORN of grade ≥1. Multivariate analysis revealed that the maxilla volume receiving more than 50 GyE (V50) and the presence of teeth within the planning target volume were significant risk factors for ORN. Dose-volume histogram analysis revealed that V10 to V50 parameters were significantly higher in patients with ORN than in those without ORN.ConclusionsV50 and the presence of teeth within the planning target volume were independent risk factors for the development of ORN after C-ion RT using a 16-fraction protocol.