Physics Contribution
Risk of Developing Second Cancer From Neutron Dose in Proton Therapy as Function of Field Characteristics, Organ, and Patient Age

https://doi.org/10.1016/j.ijrobp.2008.04.069Get rights and content

Purpose

To estimate the risk of a second malignancy after treatment of a primary brain cancer using passive scattered proton beam therapy. The focus was on the cancer risk caused by neutrons outside the treatment volume and the dependency on the patient's age.

Methods and Materials

Organ-specific neutron-equivalent doses previously calculated for eight different proton therapy brain fields were considered. Organ-specific models were applied to assess the risk of developing solid cancers and leukemia.

Results

The main contributors (>80%) to the neutron-induced risk are neutrons generated in the treatment head. Treatment volume can influence the risk by up to a factor of ∼2. Young patients are subject to significantly greater risks than are adult patients because of the geometric differences and age dependency of the risk models. Breast cancer should be the main concern for females. For males, the risks of lung cancer, leukemia, and thyroid cancer were significant for pediatric patients. In contrast, leukemia was the leading risk for an adult. Most lifetime risks were <1% (70-Gy treatment). The only exceptions were breast, thyroid, and lung cancer for females. For female thyroid cancer, the treatment risk can exceed the baseline risk.

Conclusion

The risk of developing a second malignancy from neutrons from proton beam therapy of a brain lesion is small (i.e., presumably outweighed by the therapeutic benefit) but not negligible (i.e., potentially greater than the baseline risk). The patient's age at treatment plays a major role.

Introduction

Concern has been raised about the potential for radiation-induced second malignancies when treating cancer patients with radiotherapy 1, 2, 3, 4. Sophisticated treatment techniques, such as intensity-modulated photon therapy (IMRT) and proton therapy, allow for very conformal dose distributions but can result in additional scattered radiation. In the case of 6-MV IMRT, this refers to photon radiation, and for proton therapy, it refers to secondary neutrons.

The risk of developing a second malignancy is of particular concern in pediatric patients for three reasons: (1) the long life expectancy after treatment; (2) the greater risk their organs have of developing second malignancies (5); and (3) the greater dose their organs receive, on average, compared with adult patients treated with the same fields (6). Numerous reports have been published on second malignancies from the Childhood Cancer Survivor Study 7, 8. From the study of childhood cancers, it was found that the risk of developing a second cancer in the first 25 years after treatment can be as great as 12% (9). In the volume irradiated directly by treatment fields, proton therapy can be expected to show an advantage compared with photon therapy because of the significantly reduced integral dose (10). Nevertheless, it has been discussed whether highly effective neutron radiation affecting organs further away from the treatment volume might diminish or even negate this advantage 1, 10.

During proton beam delivery, neutrons are either generated in the patient or in the treatment head, from which they can potentially reach the patient. Two treatment techniques are commonly used for proton therapy: passive scattering and pencil-beam scanning. Proton beam scanning delivers significantly less secondary dose than any other treatment modality using photons or protons (11). Because proton beam scanning is technically challenging, most patients treated with protons are still treated with passive scattering techniques, which require various scatterers, beam-flattening devices, collimators, and energy modulation devices. Additionally, for each patient, individual apertures and compensators are required. These devices through which the beam has to pass can potentially generate neutrons. Neutron doses have been measured at many facilities for different beam delivery conditions 12, 13, 14, 15, 16, 17, 18. Furthermore, Monte Carlo simulations to assess neutron doses have been done 6, 12, 19, 20, 21. Most of the published work refers to well-defined geometries and thus estimating the neutron dose as a function of the distance relative to the treated volume. Figure 1 shows the measured and calculated doses as a function of lateral distance to the field edge for various proton beams. Large variations occur because the production of neutrons depends on the material in the beam path and thus depends on the design of the beam line and the field-specific settings of the treatment head. Figure 1 also shows what to expect in terms of the scattered photon dose in IMRT (22).

Although such data are helpful for relative comparisons, detailed cancer risk estimations require organ-specific doses. Because three-dimensional dose maps in the patient cannot be measured, computer simulations have to be done. Furthermore, owing to the concern of excessive radiation with most imaging techniques, whole-body scans are rarely available, and whole-body models are needed. Previous studies have shown that to perform realistic dosimetry calculations, age-dependent phantom representations must be used (23). Realistic whole-body phantoms have been developed resembling adult (24) and pediatric patients 25, 26. With these tools, neutron doses have been assessed as a function of the patient's age, organ, and several proton field parameters 6, 19. The data demonstrated that neutron doses increase with increasing range and modulation width, decrease with field size (area covered by the aperture), and fall off rapidly as a function of distance to the target. When using passive scattered proton therapy, the main source of neutrons is typically the treatment head (i.e., external neutrons). A previous study also showed that neutron doses to specific organs depend considerably on the patient's age. The purpose of this study was to estimate the risk of developing a second cancer from scattered doses in proton therapy using previous calculations of organ-equivalent neutron doses (6).

Section snippets

Dose calculations in adult and pediatric whole-body phantoms

Monte Carlo simulations using a detailed description of the treatment head geometry were used to determine the patient field-specific proton and neutron fluence generated by the treatment head (27). Next, the Monte Carlo code was used to simulate a voxelized patient (phantom) geometry (28). We have implemented the geometry of an adult man, a 14-year-old boy, an 11-year-old boy, an 8-year-old girl (Fig. 2), a 4-year-old girl, and a 9-month-old boy. The phantoms distinguish among 23, 47, and 48

Risk dependence on age, gender, and field parameters

Fig. 3, Fig. 4 show the LAR for the three youngest and oldest phantoms, respectively, as a function of field number. The risks were calculated for a 70-Gy treatment and are the sum for all considered cancers, except for breast cancer. To disentangle the gender and age dependence of risk, we also analyzed the doses of the 4-year-old female phantom assuming the risk model parameters for males. The female had significantly greater LAR values than the male (about a factor of 2.5). The risk

Conclusion

We have investigated the dependence of lifetime risk of developing a second cancer in patients of different ages treated for a brain tumor with passive scattered proton beams. The main component of risk was due to neutrons generated in the treatment nozzle, including all patient-specific devices (i.e., brass aperture and plastic compensator) and was 82–98% of the total risk, depending on the beam parameters. An increase in treatment volume (range and modulation increase from 10/5 cm to 15/10

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    Supported in part by National Cancer Institute Grant R01 CA 116743.

    Conflict of interest: none.

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