Cancer Therapies

Carbon Ion Therapy

The clinical success of particle therapies, especially proton therapy being used throughout the world fueled interest in

clinical potential for the use of heavier ions. It was understood that heavier ions offered a higher biological impact because of their higher linear energy transferring ability.

In 1975, research into heavy-ion beams was commenced in the Lawrence Berkeley Laboratory (LBL), USA where the BEVALAC was installed. The BEVALAC is a compound accelerator capable of producing energetic charged particle beams. These high-energy ion beams have been used in multidisciplinary research related to fundamental radiobiology and cancer therapy.

About a decade later, the Japanese government began construction on the world’s first heavy-ion facility designated for medical use at the National Institute of Radiological Sciences (NIRS), attracting scientists with experience from the BEVALAC and LBL. The Heavy Ion Medical Accelerator (HIMAC) in Chiba, Japan was completed in 1993 and a year later clinical trials in carbon-ion radiotherapy (CIRT) began.

The HIMAC provided passive-beam irradiation and NIRS was the only facility for CIRT. In 1997, the GSI Carbon-Ion Radiotherapy Facility in Germany started using heavy-ion beams in clinical practice treating 440 patients with good results before its closure in 2008. Meanwhile NIRS completed development of a pencil-beam raster scanning (PBS) treatment facility in 2012, and with promising outcomes.

To date, nearly 70 protocols have been conducted at NIRS to delineate CIRT efficacy, safety, optimal treatment indications, and dose fractionation. Despite the cost, CIRT centers continue to grow worldwide. In addition, the clinical successor to the GSI Carbon-Ion Radiotherapy Facility, the Heidelberg Ion Therapy Center (HIT) is involved in testing carbon (-boost) versus other irradiation modalities.

Compared to proton therapy, CIRT provides many unique advantages: radiobiologically, carbon-ion beams result in two to three times the relative biological effect (RBE; the biological effectiveness of one type of ionized radiation relative to another, given the same amount of absorbed energy) of proton, does not show an oxygen effect, sublethal damage repair, and has less cell-cycle-related radiosensitivity. These unique characteristics formed the rationale in initially applying carbon to radioresistant and/or hypoxic disease.

With radionormal or radiosensitive disease, short-term hypofractionated treatment becomes possible, owing to diminished dose delivered to healthy tissue. More CIRT indications then became apparent – the sharp dose distribution allowed for therapeutic dose delivery to tumors which were adjacent to vital, radiosensitive organs.

These advantages have provided for hypofractionated radiotherapy of more common cancers with an improved adverse effect profile compared to conventional therapy.

The marker-less respiration-gated PBS irradiation coinciding with the target-respiratory movement has allowed for medical care of radioresistant, previously untreatable disease.

As of now, at least 10,000 patients have undergone CIRT at NIRS, with 12,000 across all facilities in Japan and over 15,000 worldwide. As early as 2003, based on the analysis of data of the first 9 years of NIRS’ clinical trials, the Japanese government allowed CIRT to be made available to the general public.

CIRT has demonstrated efficacy against prostate, head and neck, lung, and liver cancers, bone and soft tissue sarcomas, locally recurrent rectal cancer, and pancreatic cancer, including locally advanced disease.