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Abstract

This study aims to reduce the uncertainty about the photoneutron dose produced over a course of radiotherapy with high-energy photon beams and evaluate photoneutron contamination-based secondary malignancy risk for different treatment modalities. Dosimetric measurements were taken in Philips SL25/75, Elekta Synergy Platform (Elekta AB, Stockholm, Sweden), Varian Clinac DHX High Performance systems (Varian Medical Systems, Palo Alto, CA), and Cyberknife Robotic Radiosurgery Unit (Accuray Inc., Sunnyvale, CA) using bubble detector for neutron dosimetry. The measurement data were used to determine in-field and out-of-field neutron equivalent dose in 6-MV 3D conformal radiotherapy, sliding window–intensity-modulated radiotherapy, and stereotactic body radiotherapy and to calculate the effective dose in 18-MV 3D conformal radiotherapy and sliding window–intensity-modulated radiotherapy techniques for patients with prostate cancer undergoing a standard treatment. For the 18-MV treatment techniques, the secondary malignancy risk due to the neutron contamination was estimated using the risk factors published by The International Commission on Radiological Protection. The neutron contamination-based secondary malignancy risk for the 18-MV 3D conformal radiotherapy and sliding window–intensity-modulated radiotherapy modalities was found to be 0.44% and 1.45% for Elekta Synergy Platform and 0.92% and 3.0% for the Varian Clinac DHX High Performance, respectively. For 6-MV 3D conformal radiotherapy, sliding window–intensity-modulated radiotherapy, and stereotactic body radiotherapy treatment techniques, neutron equivalent doses inside the treatment field were found to be lower than 40 mSv. Our measurements reveal that equivalent dose and effective dose due to the neutron contamination are at a considerable level for 18-MV sliding window–intensity-modulated radiotherapy treatments, while 6-MV photon beams used in different modalities still induce only negligible photoneutrons. The secondary malignancy risk based on photoneutron should be therefore taken into consideration in case of selecting 18-MV photons in a sliding window–intensity-modulated radiotherapy treatment instead of 6 MV.

Keywords

neutron contamination photoneutron dose linear accelerator bubble detector

Introduction

With the advance in technology, new treatment modalities, such as intensity-modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT), have been getting widespread. Although these new treatment techniques have an advantage in tumor coverage and normal tissue sparing, they cause an increase in total monitor unit (MU).^1
–3 With the higher total MU, total body dose is also getting increased and thus secondary malignancy risk due to the radiotherapy can become relatively considerable.^4
–6 In addition to primary photon or electron beam, neutrons are generated by nuclear reactions in high-energy radiotherapy facilities if the energy of an incident photon or electron is higher than the threshold energy for photonuclear or electronuclear reactions.^7,8 A neutron called as “a photoneutron” or “an electroneutron” is generated by an interaction of a high-energy incident photon or electron with the heavy metals in the heads of linear accelerators, and thus an unaccounted additional neutron dose is exposed to a patient over a course of treatment.⁹

For the photon energies below 8 MeV, photoneutron dose is mostly neglected due to the lower photonuclear cross sections of the heavy metals in the heads of linear accelerators at these energy levels.¹⁰ However, as far as we know, there is no information about whether these values are still negligible for 6-MV IMRT and SBRT modalities or not. In SBRT facilities, especially in Cyberknife, total irradiation time is about 40 000 MU for patients with prostate cancer undergoing standard treatment. Moreover, in some treatment cases such as deeply seated lung tumor, it goes to over 70 000 MU depending on the depth of the treatment volume and prescription dose like 60 Gy/3fr. Therefore, it causes new uncertainty about the amount of photoneutron dose in 6-MV SBRT facilities. In the literature, there are several studies about the photoneutron dose measurement, with different dosimetric systems such as bubble detector, thermoluminescance dosimeter, activation detector, and polycarbonate film.^{6,7,9,11

–17} However, there is sparse information about the secondary malignancy risk due to the neutron contamination in 18-MV 3D conformal radiotherapy (3D-CRT) and sliding window (SW)–IMRT treatment techniques. In this study, we therefore investigate the photoneutron-based secondary malignancy risk created using 18-MV photon beams in 3D-CRT and SW-IMRT treatments. Moreover, we measure and evaluate the amount of photoneutron dose generated in 6-MV 3D-CRT, SW-IMRT, and SBRT modalities.

Materials and Methods

Dosimetric measurements were taken in the Department of Radiation Oncology at Hacettepe University using 4 radiation therapy systems, that is, Philips SL25, Elekta Synergy Platform, Varian Clinac DHX High Performance, and CyberKnife Robotic Radiosurgery Unit. Since the photoneutron dose equivalent is predominantly from fast neutrons, the evaluation of neutron dose equivalent was performed using bubble detectors for neutron dosimetry (BD-PND) with a size of 145 mm in length and 19 mm in diameter (Bubble Technology Industries [BTI], Chalk River, Canada). Bubble detectors consist of superheated liquid droplets dispersed in a holding transparent polymer material. In the absence of a neutron field, these microdroplets are capable of remaining in the liquid state above their normal boiling point over a several months. These liquid droplets, however, vaporize to form bubbles when exposed to energetic neutron particles. The number of bubbles is proportional to the equivalent neutron dose. The counting process can be performed by the naked eye or the automatic bubble detector reader (BDR-III; BTI).^11
–13 Additionally, this type of detector is not sensitive to photon energy below 25 MV, while its neutron threshold energy is 100 keV with a reasonably flat dose equivalent response from 200 keV to 15 MeV. It is, therefore, only sensitive to fast neutrons.^6,12 The sensitivity of the detector is 5 to 10 bubble/mrem.¹⁸ Each detector has a different sensitivity value specified on a bubble detector itself and in the calibration certificate given by BTI. In the present study, bubbles generated in the detector were counted and analyzed with BDR-III. Each measurement was repeated 3 times to take an average and thus reduce random errors of a single measurement.

Although bubble detectors reported as one of the most sensitive and accurate neutron dosimeter, it has several disadvantages or limitations. One of them was a limited dynamic range of the detector. When the number of bubbles exceeded about 300, bubbles began to overlap during the analysis of the BD-PND.¹⁶ The accuracy of bubble detector, therefore, was decreasing with increasing number of bubbles over 300. Manufacturer, further, recommended that the number of bubbles should be kept in the range of 80 to 120 to get high accuracy in dose reading. For that reason, we gave importance to keep the number of bubbles in recommended range. Moreover, each detector was analyzed after 10 minutes of standing following exposure. After reading process, detectors were recompressed to transform the bubbles back into droplets, and then 1 hour of standing was allowed before next exposure to yield optimum detector performance.¹²

Measurement Setup for 6-MV Photon Energy

The measurement setups for 6-MV photon energy were built to investigate the photoneutron dose inside and outside the treatment field for different treatment modalities. In the measurements, the source-to-surface distance (SSD) was set to 80 and 100 cm for Cyberknife and the other 3 systems, respectively. The largest cone of 60 mm was selected to shape the treatment field of Cyberknife, whereas the field of 10 ×10 cm² was used for the other systems, and irradiation was performed at 0° of gantry angle. The bubble detectors were placed both on the central axis of a treatment field and 10 cm distance from the field edge on the same horizontal plane. The distance between the 2 detectors was determined by taking the midpoint of the detector as a reference point. In addition to free-in air measurement, photoneutron contamination at 1-cm depth was analyzed using RW3 solid water phantom. Measurements were repeated for 100 and 500 MU. Following the measurements, both of these values were compared via normalization to 1 MU in order to analyze that the neutron contamination measurements show linearity with irradiation time and/or MU. These measurement results were also used to estimate in-field and out-of-field neutron equivalent doses for a typical treatment plan of a patient with early-stage prostate cancer.

Measurement Setup for 18-MV Photon Energy and Secondary Malignancy Risk Evaluation

Neutron dose was measured in the 2 linac systems with 18-MV photon energy option, that is, the Elekta Synergy Platform and the Varian Clinac System using BD-PND. Measurement setups for 18-MV photon energy were specified in Table 1. In our scenario, we aimed to estimate the photoneutron-based organ equivalent doses and effective dose for a typical patient with prostate cancer treated with 3D-CRT and SW-IMRT modalities using 18-MV photon energy. To evaluate the neutron-equivalent dose, measurements were taken at different depths and different distances from the isocenter using RW3 solid water phantom (Table 1). The 3D-CRT and SW-IMRT irradiation were only delivered at 0° gantry angle due to the limited dynamic range of bubble detector. The relative locations of critical organs with respect to the target prostate volume were determined by an experienced physician using computed tomography images of Alderson Rando phantom (Radiology Support Devices, Inc, Long Beach, California). The organ equivalent doses due to the neutron contamination were estimated by interpolation and extrapolation of the detector readings at the listed reference points. After these processes, the organ equivalent and effective doses throughout the treatment were calculated based on the prescribed doses of 70 and 76 Gy for 3D-CRT and SW-IMRT, respectively. These dose values were the standard Planning Target Volume (PTV) doses prescribed for a case with early-stage prostate cancer in our clinics. Finally, we estimated the risk of secondary malignancies due to the neutron contamination using the International Commission on Radiological Protection (ICRP) report 103.¹⁹ This report suggests calculating the secondary malignancy risk as 5% per sievert (Sv) of effective dose.

Table 1.

The Methodology for Photoneutron Contamination Measurements for 18-MV Photon Beams.

Photoneutron Measurements
Linacs	Varian Clinac DHX, Elekta Synergy Platform
Energy	18 MV
SSD	100 cm
Field size	10 × 10 cm
Ganrty angle	0°
Phantom material	RW3 solid water phantom
Depths	0, 1, 5, and 10 cm
Distance from axis	0, 10, 20, 50, and 80

Abbreviation: SSD, source surface distance.

Results

Photoneutron doses for 6-MV photon beams were found to be 6.62 × 10⁻⁴ mSv/MU, 4.75 × 10⁻⁴ mSv/MU, 8.85 × 10⁻⁴ mSv/MU, and 3.70 × 10⁻⁴ mSv/MU at the central axis of treatment field and the depth of 0 cm for Philips SL25, Elekta Synergy Platform, Varian Clinac DHX High Performance Systems, and CyberKnife Robotic Radiosurgery Unit, respectively. Photoneutron dose normalized to 1 MU agreed within 1% for 100 and 500 MU in all systems. However, out of the treatment field and at 1-cm depth on the central axis, BD-PND detectors did not detect any neutron dose for the all treatment modalities using 6-MV photon energy. Therefore, measurements were not performed at the depths of 5 and 10 cm on the central axis and at different distances of 20, 50, and 80 cm from the field edge. As illustrated in Table 2, neutron-equivalent doses inside the treatment field were estimated as lower than 40 mSv for typical prostate cancer treatment using 6-MV 3D-CRT, SW-IMRT, and SBRT treatment modalities. While the quantities of photoneutron doses for all modalities were at a negligible level, the SW-IMRT treatments caused almost 4 times higher doses than 3D-CRT treatments due to increased total MU. Neutron contamination generated in the Cyberknife unit was higher than that in 3D-CRT modalities while lower than that in SW-IMRT modalities for the possible treatment systems.

Table 2.

Neutron Equivalent Dose (mSv) Inside the Treatment Field for Patient With Prostate Cancer Using 6-MV Photon Beams.

	Radiotherapy Technique
	3D-CRT	SW-IMRT	SBRT
Prescription dose	2 Gy/fr, 70 Gy	2 Gy/fr, 76 Gy	7.3 Gy/fr, 36.5 Gy
MU/fr	300	1000	6800
Total MU	10 500	38 000	34 000
Linear accelerators	Total neutron equivalent dose (mSv) = mSv/MU^a × total MU
Philps SL25/75	6.95	.............	.............
Varian Clinac	9.29	33.63	.............
Elekta Synergy	4.98	18.05	.............
Cyberknife	.............	.............	12.58

Abbreviations: 3D-CRT, 3D conformal radiotherapy; SW-IMRT, sliding window–intensity-modulated radiotherapy; SBRT, stereotactic body radiotherapy; MU, monitor unit.

^amSv/MU represents the photoneutron dose measured inside of the treatment field at phantom surface.

Contributions of selected organs to effective dose and total effective dose calculated per fraction of 18-MV 3D-CRT and SW-IMRT treatments are summarized in Table 3. The estimated effective doses due to the neutron contamination were considerably higher in SW-IMRT than in 3D-CRT treatments. The secondary malignancy risk estimation for 3D-CRT and SW-IMRT was found to be 0.44% and 1.45% for Elekta system and 0.92% and 3.0% for the Varian system, respectively. Although the photon energy used in measurement setup was the same for both linacs, estimated effective doses were almost 2 or 3 times higher in Varian Clinac than that in Elekta Synergy (Table 3). Another noteworthy point was that, in IMRT treatment, photoneutron dose increased almost 3 times with respect to 3D-CRT in both linacs. It could be directly connected to prolonged irradiation time in IMRT technique. Additionally, as illustrated in Table 3, individual contributions of bone marrow and breast to effective dose were almost 9% in Varian linac and 7.5% in Elekta linac for both treatment modalities of 3D-CRT and SW-IMRT.

Table 3.

Effective Dose due to the Photoneutron Contamination per Fraction of 3D-CRT and SW-IMRT Using 18-MV Photon Beams.

	Linear Accelerators
	Elekta Synergy Platform		Varian Clinac DHX High Performance
MU/fr—Technique	600 MU—SW-IMRT	200 MU—3D-CRT	600 MU—SW-IMRT	200 MU—3D-CRT
Total MU—# of fr	22 800 MU—38 fr	7000 MU—35 fr	22 800 MU—38 fr	7000 MU—35 fr
Organ and tissues	Effective dose’ = WT × HT/fr (mSv × 10⁻²)^a
Bone marrow (red)	57.6	19.2	136.8	45.6
Lungs	21.6	7.2	50.4	16.8
Breast	54.1	18.0	144.0	48.0
Throid	12.0	4.0	26.4	8.8
Skin	9.0	3.0	20.6	6.9
Remainder tissues^b	609.1	203.0	1203.6	400.4
Total effective dose^c/fr	763.4	254.4	1581.8	526.5

Abbreviations: WT, tissue weighting factor, HT/fr, organ equivalent dose per fraction; E, effective dose; WR, radiation weighing factor DT, R, absorbe dose; MU, monitor unit; 3D-CRT, 3D conformal radiotherapy; SW-IMRT, sliding window–intensity-modulated radiotherapy.

^a Effective dose’: Contribution of each organ to total effective dose

^bRemainder tissues: stomach, adrenals, heart, kidneys, oral mucosa, pancreas, prostate, brain, small intestine, bladder, testis, liver, esophagus, parotid glands.

^cTotal effective dose: $E = \sum W_{T} \sum W_{R} D_{T, R}$ .

Discussion

With the use of new treatment techniques in radiotherapy facilities, survival times of the patients with cancer have extended many years.²⁰ Brenner et al reported that the estimated secondary malignancy risk was 1 in 290 for all patients having prostate cancer treated with radiation therapy, while it increases up to 1 in 70 for long-term survivors (≥10 years).²¹ Therefore, evaluation of secondary malignancy risk after radiotherapy has been more necessary, especially for cancer types with long survival times such as prostate cancer.

In the literature, there are many studies about whether the use of high-energy photon beams in IMRT facility considerably causes an increase in secondary malignancy risk or not. Schneider et al ²² estimated that 6-MV IMRT treatment increases secondary malignancy risk by almost 15% with respect to 15-MV conventional 4-field treatment, while the risk increases from 15% to 20% and 60% for 15-MV and 18-MV IMRT treatments, respectively. However Kry et al ²³ reported that, according to Monte Carlo calculations, there is no significant difference in the risk of secondary malignancy between high-energy and low-energy IMRT treatments. The reason of this situation is explained as that high-energy therapy requires lower MUs to deliver a comparable dose to target volume with respect to low-energy therapy, and thus scattered photon dose in high-energy IMRT is at a lower level than that in low-energy IMRT. However, during the use of high energy in prostate IMRT treatment, distant critic organs from the treatment region like thyroid and lungs receive higher photoneutron dose. Therefore, in this study, we focused on the effects of neutron contamination on total body dose and secondary malignancy risk. Our measurements results show that 18-MV SW-IMRT treatment of a patient with prostate cancer increases the photoneutron-based effective dose almost 3 times with respect to 3D-CRT treatment. In measurements for 6-MV treatments, neutron equivalent dose inside the treatment field is always under the level of 40 mSv for all treatment modalities, while SW-IMRT almost triple neutron dose with respect to 3D-CRT. Therefore, the choice of IMRT modality as the treatment technique instead of 3D-CRT requires considering the increase in photoneutron dose of total body and critic organs even located in a region of low-level photon radiation since the prolonged irradiation time or MUs.

Hall et al ⁴ evaluated the secondary malignancy risk in patients with prostate cancer treated with 6-MV conventional radiotherapy and IMRT. They found the risk as 1.5% and 3%, respectively. Similarly, Kry et al ⁵ also focused on the radiation-induced secondary malignancy risk after radiotherapy in patients with prostate cancer treated with IMRT using different photon energies of 6, 10, 15, and 18 MV in Varian linac and photon energies of 6 and 18 MV in Siemens linac (Siemens Medical Solutions USA, Inc. Malvern, PA). In this study, secondary malignancy risks were estimated as 2.9%, 2.1%, 3.4%, and 5.1% for 6, 10, 15, and 18 MV in Varian linac, respectively. Moreover, Siemens linac created the risks of 3.7% and 4.0% for 6-MV and 18-MV treatments, respectively. In the study performed by Kry et al,⁵ secondary malignancy risk values for the same energy level show differences between various linac models. In our study, the secondary malignancy risk based on neutron contamination for Varian linac was similarly found 2 times higher than that for Elekta linac in 18-MV photon energy. Although the working principle and general design of linear accelerators show similarity, configuration and specification of the components used in the linac head show distinctive characteristics from one model to another.^24,25 Therefore, secondary malignancy risk based on photon and/or photoneutron dose depends on both linac model and treatment energy used. Furthermore, photoneutron component of effective dose ascends by switching the treatment energy from 6 MV, at negligible level, to 18 MV. Photon component of effective dose, however, decreases with treatment energy due to the lower irradiation time or MU in higher photon energies. For instance, Kry et al reported secondary malignancy risk as 2.9% and 5.1% for 6-MV and 18-MV IMRT techniques in Varian linac, respectively. The first risk value had only photon component due to the negligible level of neutron contamination at 6-MV photon energy. However, the risk of 5.1% included both photon and photoneutron component of the effective dose. In our study, we calculated the risk as 3%, for only photoneutron component of effective dose, in a Varian linac for 18-MV IMRT technique. Therefore, the photon component of secondary malignancy risk could approximately be calculated by subtracting the estimated value, 5.1%, by Kry et al from our calculated risk, 3%. This value was approximately equal to 2.1%, and thus it was lower than 2.9% as expected.

One of the most challenging issues with analysis study on secondary cancer risk is to support the dosimetric measurements with the statistical data acquired by following up patients with cancer for sufficient time, maybe decades, to observe the cancerous effect of diverse radiation types and energies. Our estimations and risk analyses depend on the ICRP risk factors derived from the follow-up studies on survivors of the past nuclear accidents and atomic bombs.

Conclusion

In spite of the deficiency of statistical cohort studies, our estimation analysis carries an opportunity of comparison of photoneutron doses and secondary malignancy risks based on photon energy, treatment modality, and system. Our measurement results and risk analyses show equivalent dose and effective dose due to the neutron contamination cannot be neglected in 18-MV SW-IMRT facilities. Therefore, one should consider the contribution of photoneutrons on the secondary malignancy risk in case of using 18 MV in SW-IMRT applications. Although a slight amount of photoneutrons is generated using 6-MV photon energy, it should not be completely neglected in clinical applications.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK 1002 Project: 109S488) and Hacettepe University Scientific Research and Development Office (HURDO Support Project: 09D09101004 and Grant Project: 1-05 A 101 009).

Abbreviations

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Evaluation of Photoneutron Dose Measured by Bubble Detectors in Conventional Linacs and Cyberknife Unit

Abstract

Keywords

Introduction

Materials and Methods

Measurement Setup for 6-MV Photon Energy

Measurement Setup for 18-MV Photon Energy and Secondary Malignancy Risk Evaluation

Results

Discussion

Conclusion

Footnotes

Declaration of Conflicting Interests

Funding

Abbreviations

References