Radiation-Induced Cancers From Modern Radiotherapy Techniques: Intensity-Modulated Radiotherapy Versus Proton Therapy

Purpose

To assess and compare secondary cancer risk resulting from intensity-modulated radiotherapy (IMRT) and proton therapy in patients with prostate and head-and-neck cancer.

Methods and Materials

Intensity-modulated radiotherapy and proton therapy in the scattering mode were planned for 5 prostate caner patients and 5 head-and-neck cancer patients. The secondary doses during irradiation were measured using ion chamber and CR-39 detectors for IMRT and proton therapy, respectively. Organ-specific radiation-induced cancer risk was estimated by applying organ equivalent dose to dose distributions.

Results

The average secondary doses of proton therapy for prostate cancer patients, measured 20–60cm from the isocenter, ranged from 0.4 mSv/Gy to 0.1 mSv/Gy. The average secondary doses of IMRT for prostate patients, however, ranged between 3 mSv/Gy and 1 mSv/Gy, approximately one order of magnitude higher than for proton therapy. Although the average secondary doses of IMRT were higher than those of proton therapy for head-and-neck cancers, these differences were not significant. Organ equivalent dose calculations showed that, for prostate cancer patients, the risk of secondary cancers in out-of-field organs, such as the stomach, lungs, and thyroid, was at least 5 times higher for IMRT than for proton therapy, whereas the difference was lower for head-and-neck cancer patients.

Conclusions

Comparisons of organ-specific organ equivalent dose showed that the estimated secondary cancer risk using scattering mode in proton therapy is either significantly lower than the cases in IMRT treatment or, at least, does not exceed the risk induced by conventional IMRT treatment.

Introduction

Protons are used in radiotherapy because of their advantageous physical properties. These include a near-zero exit or distal dose just beyond the target volume, resulting in reduced proton doses to normal tissue, with better conformation of the dose to the target volume. Although the sharpness of the penumbra in proton beams decreases with the depth of penetration, the penumbra is generally smaller for proton than for photon beams, up to approximately 17 cm, resulting in higher conformity of the former 1, 2, 3, 4. In general, tumors in cancer patients undergoing radiation treatment are exposed to high doses (prescription dose), whereas the surrounding normal tissues are exposed to intermediate doses, and the rest of the body is exposed to low doses. Exposure of normal tissues to intermediate doses is due to the primary radiation in the beam path, whereas exposure of the rest of the body to low doses is due primarily to out-of-field radiation resulting from scattering and leakage. Although intensity-modulated radiotherapy (IMRT) can produce the same level of dose conformity in the tumor, it may expose normal tissue to higher intermediate or low doses, resulting in higher secondary exposure (5). In contrast, although proton therapy may result in reduced exposure of adjacent normal tissue to intermediate doses, it may lead to an increase in low doses to the rest of the body, due to the number of neutrons produced by the scattering components of passively scattered proton beams, which may exceed that produced by conventional photon treatment. Thus, proton therapy may have a higher risk of radiation-induced secondary cancers than photon therapy, diminishing the superiority of proton therapy.

To date, there have been many measurements and calculations of secondary neutron doses resulting from clinical proton beams 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23. For example, a comparison of secondary neutron dose in proton treatment with secondary photon dose in photon radiation treatment found that proton therapy in the scattering mode yielded much higher secondary doses than did conventional IMRT (6). The neutron dose associated with conventional proton therapy, however, is highly facility dependent and is based on various factors, including initial beam, field-shaping devices, aperture, and treatment volume 8, 9, 10, 11, 18, 19, 20, 21, 22. Calculations of secondary cancer should also include intermediate dose–induced carcinogenesis, because the risk of radiation-induced carcinogenesis due to intermediate doses in the beam path (in-field) may be much higher than that due to low doses in the out-of-field region 8, 9, 18.

Thus, intermediate dose may be more important than low dose for comparing secondary cancer risks among treatment modalities. The risks of proton therapy may therefore not exceed those of conventional IMRT treatment, because the intermediate dose of the former will be generally lower than that of the latter.

In comparing the radiation-induced secondary cancer risks of proton therapy and conventional photon therapy, it is necessary to make neutron measurements using realistic anthropomorphic phantoms. These models are needed to more accurately estimate organ doses and thus estimate risks outside of the radiation field, resulting in more realistic determinations of neutron dose distribution in patients. It is also necessary to include the risks of radiation-induced carcinogenesis in the beam path, by direct comparison of dose distributions from treatment planning. Moreover, comparisons of secondary cancer risk should include an appropriate radiation method. In this study, we compared the secondary radiation dose distribution resulting from proton treatment using a scattering mode and IMRT treatment in patients with prostate and head-and-neck cancers. On the basis of these measurements, we estimated and compared the secondary cancer risk resulting from these two treatment modalities using the concept of organ equivalent dose (OED) for radiation-induced cancer.