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Solid state diode – Ionization chamber method for measuring out-of-field neutron dose in proton therapy
Radiation Measurements 46 (2011) 1638e1642
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Radiation Measurements journal homepage: www.elsevier.com/locate/radmeas
Solid state diode e Ionization chamber method for measuring out-of-field neutron dose in proton therapy A.L. Ziebell a, *, B. Clasie c, A. Wroe d, R.W. Schulte d, M.I. Reinhard b, S.J. Dowdell a, M.L. Lerch a, M. Petasecca a, V.L. Perevertaylo e, O.S. Zinets f, I.E. Anokhin f, A.B. Rosenfeld a a
Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia Australian Nuclear Science and Technology Organisation, Lucas Heights, Sydney, Australia Massachusetts General Hospital and Harvard Medical School, Boston, USA d Loma Linda University Medical Center, Loma Linda, USA e SPA BIT, Ukraine f Institute for Nuclear Research, Kiev, Ukraine b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 November 2010 Received in revised form 17 April 2011 Accepted 7 May 2011
In proton therapy neutrons are introduced to out-of-field regions inside the patient. Clinicians would like to know the absorbed dose being deposited by neutrons separately to that from protons, so as to be able to directly apply their own dose equivalent weighting factors based on their opinion of the biological risk posed by neutrons in this region. The purpose of this study is to investigate a novel approach to experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions. The method pairs specially designed silicon PIN diodes with a standard clinical ionization chamber. The sensitivity of the Si diode to non-ionizing energy losses in silicon is exploited, and can be quantified by measuring the shift in forward voltage for a fixed injection current, pre and post irradiation. The mathematical relations that describe the response of the diode and the ionization chamber can be solved simultaneously to give the contributions to the absorbed dose from protons and neutrons separately. Experimental measurements were made at the Loma Linda University Medical Center (LLUMC), Loma Linda, and Massachusetts General Hospital (MGH), Boston, proton therapy facilities. Experimental separation of the partial proton and neutron contributions to the absorbed dose measured at positions lateral to a typical prostate therapy treatment field delivered to a Lucite phantom was successfully performed and compared with results from a GEANT4 simulation. The experimental results matched well with simulation confirming the validity and promise of the novel approach. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Out-of-field dosimetry Silicon diode Proton therapy Neutron dose
1. Introduction Proton therapy represents a major advance in radiation therapy (Smith, 2009). Unlike photons, protons deliver a maximum absorbed dose to tissue at the end of their range. This peaked dose, the Bragg peak, allows for a highly conformal treatment to be delivered to the tumor volume while providing maximal sparing to healthy tissue distal to the target. To achieve uniform coverage of the tumor volume, passive scattering or active beam scanning methods may be used to deliver treatment to the patient. Passive scattering systems employ a number of beam modification devices. Inelastic proton interactions with beam modification devices result in the production of high energy neutrons, which may enter the patient.
* Corresponding author. Tel.: þ61 2 4221 4574. E-mail address: [email protected] (A.L. Ziebell). 1350-4487/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.radmeas.2011.05.022
Neutrons have a higher relative biological effectiveness (RBE) than both photons and high energy primary scattered protons due to the production of low energy protons in elastic scattering reactions with hydrogenous material, along with the production of other high LET secondaries. Neutrons may play an important role in the induction of second cancer following treatment. Dose equivalent measurements are a method of quantifying the biological risk posed by radiation in out-of-field regions of proton therapy (Yan et al., 2002; Hall, 2006; Wroe et al., 2007, 2009). When calculating dose equivalents, radiation protection weighting factors and quality factors recommended by the ICRP or ICRU (ICRP 92, 2003; ICRU 36, 1983) may be used, depending on the approach taken. Both these weighting factors scale an absorbed dose in Gy, to the dose equivalent in Sv. Most commonly, an average factor is applied to the absorbed dose deposited by all particles at the site of interest. Bonner spheres are capable of measuring the dose equivalent from neutrons only (Yan et al., 2002), but have a poor spatial
A.L. Ziebell et al. / Radiation Measurements 46 (2011) 1638e1642
resolution and are not suitable for measurements near the field edge. Currently recommended weighting factors for individual particles in proton therapy are discussed in the literature (Xu et al., 2008; Brenner and Hall, 2008). Energy-averaged neutron weighting factors are typically between 2 and 11 and possibly as high as 25 in low dose regions. Limited data from human exposure to neutrons makes accurate determination of the neutron RBE for clinical endpoints difficult (Brenner and Hall, 2008). To have a greater control on quantifying the risk posed by neutrons, clinicians would like to know the absorbed dose deposited by neutrons separately from that deposited by protons, and from there assign their own neutron specific weighting factors based on experience with patient treatments. This approach is becoming more desirable as our understanding of radiobiology in therapy increases. At present, experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions is a challenging task. The absorbed dose deposited by protons produced in neutron elastic scattering reactions cannot be distinguished from the absorbed dose deposited by protons scattered from the primary beam. With Monte Carlo radiation transport codes such as the GEANT4 toolkit, individual particles can be tracked and the absorbed dose deposited by neutrons at outof-field positions can be recorded separately from that due to protons. Recently, a GEANT4 study was performed to obtain the partial proton and neutron contributions to the absorbed dose at out-of-field positions in a Lucite phantom for a typical prostate therapy treatment delivered using passive techniques (Clasie et al., 2010). Experimental verification of the partial proton and neutron contributions to the absorbed dose were not possible with any of the experimental techniques available. In this study a novel experimental approach to separating the proton and neutron contributions to the absorbed dose in mixed photon, proton and neutron fields is introduced. The approach pairs a specially designed silicon PIN diode with a standard clinical ionization chamber. The diode can be used to measure the effects of non-ionizing energy losses (NIEL) in silicon. Previously, such a diode has been paired with activation foils to verify Monte Carlo simulations in neutron fields (Carolan and Rosenfeld, 2006). In this work the suitability of the proposed paired dosimeter method to out-of-field dosimetry in proton therapy is discussed, and the method is used to separate the partial contributions of protons and neutrons to the absorbed dose at points along a series of measurements lateral to the field edge of a typical prostate therapy treatment delivered to a Lucite phantom using passive techniques. These experimental results are compared with results from the previously mentioned GEANT4 simulation by Clasie et al. (2010).
1639
displacement damage cross section (Vasilescu and Lindstroem, 2000), which has units of cm2keV/g; and depends on the spectral fluence of particle type i incident on the diode. The measured forward voltage shift is given by equation (1), where l is a diode specific constant related to the base length, resistivity and recombination properties of the diode (Swartz and Thurston, 1965; Rosenfeld et al., 1990), in units of V/Gy, Dmtrl,i is the absorbed dose in the phantom material when the detector is replaced by phantom material, in units of Gy and Fi,1Gy(mtrl)(E) is the spectral fluence normalized to the spectral fluence required to deposit an absorbed dose of 1 Gy in the phantom material, in units of cm2 Gy1. For a mixed radiation field, the total shift in forward voltage, DVF, is the sum of all DVF,i
DVF;i ¼ l$Dmtrl;i
X
KSi;i ðEÞ$Fi;1GyðmtrlÞ ðEÞ
(1)
From here on, DVF,i/Dmtrl,i will be referred to as the sensitivity of the diode to particles of type i. In Fig. 1 KSi,i(E)$FiE,1Gy(TE) is shown where KSi,i is as described above, and Fi,E,1Gy(TE) is the fluence of particle type i with energy E required to deposit 1 Gy in adipose tissue, for both protons and neutrons separately. It can be seen that for the energy range relevant to proton therapy, KSi,i(E)$Fi,E,1Gy(TE) for neutrons is 10e100 times greater than KSi,i(E)$Fi,E,1Gy(TE) for protons. Thus when operating in NIEL mode, the sensitivity of the diode to neutrons is expected to be 10e100 times the sensitivity of the diode to protons, for the same absorbed dose in tissue. A big advantage of using this diode in a mixed photon, proton and neutron field, is that the sensitivity of the diode to the same absorbed dose in Lucite from photons is three orders of magnitude less than the sensitivity of the diode to fast neutrons (Rosenfeld et al., 1999), thus the response of the diode in out-of-field regions in proton therapy will be mostly due to the induced displacement damage effects resulting from the fluence of protons and neutrons. 2.2. Separating the proton and neutron absorbed dose The response of the aforementioned diode and a standard clinical ionization chamber are described in equations (2) and (3) assuming a mixed proton-neutron field. Both are functions of the
2. Materials and methods 2.1. Radiation damage in Si diodes When silicon devices are exposed to a radiation field, nonionizing energy losses (NIEL) may occur that lead to atom displacements in the silicon bulk. These non-ionizing effects are quantified in terms of displacement KERMA: the kinetic energy imparted to the displaced atoms as a result of interaction with the incident particle. Deposition of displacement KERMA in the silicon diode produces a change in the resistivity of the diode base and alters the minority carrier lifetime, changing the electrical characteristics of the diode (Swartz and Thurston, 1965; Rosenfeld et al., 1990). As a result a shift in the forward voltage of the diode, DVF, is measured for the same current injected pre and post irradiation. In a mixed radiation field, the forward voltage shift of the diode due to a particle of type i with energy E is due to the displacement KERMA of that particle in Si, KSi,i(E), determined by the
Fig. 1. KSi,i(E)$Fi,E,1Gy(TE), the sensitivity of a given diode to a particle of interest, considering the fluence of particle type i with energy E required to deposit 1 Gy in adipose tissue, for both protons and neutrons separately. It can be seen that for the energy range of interest the sensitivity of the diode to neutrons is expected to be 10e100 times the sensitivity of the diode to protons, for the same absorbed dose in tissue.
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A.L. Ziebell et al. / Radiation Measurements 46 (2011) 1638e1642
absorbed dose deposited in the material of interest by protons and neutrons respectively.
DVF ¼ aDp þ bDn
(2)
DIC ¼ Dp þ Dn
(3)
Here a and b are the sensitivities of the diode to protons and neutrons respectively. The units of both are V/Gy. DVF and DIC are the measured forward voltage shift of the diode, and the absorbed dose in the phantom material as measured by the ionization chamber (IC), at the same point of interest. Dp and Dn are the respective proton and neutron deposited absorbed doses at this point. This expression for DIC does not explicitly include photon dose, which will of course be a component in any experimental DIC measurement using the ion chamber, but the photon component of the absorbed dose has been found to be negligible in out-of-field regions in passively delivered treatments (Clasie et al., 2010). Solving equations (2) and (3) provides separate analytical expressions for the neutron and proton absorbed doses in the material, Dp and Dn, in terms of the measurable quantities DVF, a, b and DIC. 2.3. Tissue equivalency of the Si diode GEANT4 simulations have shown that for out-of-field regions, neutrons of energy 0.15e20 MeV dominate the neutron fluence spectrum (Simpson, 2011). In this energy range, Si diodes operated as per the method described above are suitable for dosimetry applications due to the ratio of displacement KERMA in Si to neutron KERMA in tissue being approximately constant within 15%. Further, these diodes have been successfully used for tissue equivalent neutron dosimetry in fast neutron therapy (FNT) where the average energy of the neutron spectrum, 20 MeV, is similar to that found in out-of-field regions in proton therapy (Yudelev et al., 2004). 2.4. Experimental setup Experiments were carried out at the Loma Linda University Medical Center (LLUMC) and the Massachusetts General Hospital (MGH) proton therapy facilities. The diodes were ion implanted bulk PIN diodes with a base length of approximately 1 mm and pþ and nþ cross sections equal to 1.2 mm2. Each diode was housed in a Lucite probe of dimensions 50 28 200 mm3. All out-of-field measurements were performed at the Francis H. Burr Proton Therapy Center, MGH, for a typical passively scattered prostate therapy treatment delivered into a Lucite phantom. The range of the proton beam was 28 cm in water, with an 8 cm modulation and a 3.8 cm radius circular field size. The diodes were placed within the phantom at distances of 2.5, 12.5 and 22.5 cm lateral to the field edge, all at a water equivalent depth (WED) of 19 cm. After the diodes were irradiated they were removed and an Extradin T1 miniature Shonka thimble ionization chamber with 0.056 cm3 sensitive volume (SV), also housed in a Lucite probe, was placed at the former position of each diode and the same treatment was delivered to the phantom. The reproducibility of treatment delivery at this facility is within 0.5%. Post measurement DVF and DIC were normalized to the dose deposited to the spread out Bragg peak (SOBP) during the measurement. The separation of the absorbed dose contributions from neutrons and protons was calculated by solving equations (2) and (3). Results are presented in Fig. 2 and compared with the results from the GEANT4 Monte Carlo simulation by Clasie et al. (2010) in Fig. 3. In the simulation a similar proton therapy treatment was delivered to a Lucite phantom, and tracking was activated for protons, neutrons, electrons and
Fig. 2. The absorbed dose to Lucite per 1 Gy absorbed dose to the SOBP as measured by the ionization chamber, and as derived for protons and neutrons separately using equations (2) and (3).
photons. Voxels for recording the dose were located at different lateral distances from the field edge, at a WED of 22.3 cm. More details on this simulation can be found in (Clasie et al., 2010). 3. Results and discussion 3.1. Response of the Si diodes to neutrons and protons The sensitivity of each diode to neutrons, b, was measured by exposing the diodes to a neutron field obtained by delivering a 205 MeV proton beam into a 6.5 cm thick brass block which attenuated all protons. The diodes were each housed within their Lucite probe and the probes were placed between two 5 cm thick polystyrene blocks. The center of the diodes was a distance of 30.5 cm from the end of the brass beam block. The measured sensitivity of each diode was recorded. Calibration of the diodes in terms of a was performed along the central axis of a 225 MeV
Fig. 3. The partial contribution to the absorbed dose to Lucite from protons and neutrons as obtained through the simulated GEANT4 study and as experimentally derived using equations (2) and (3).
A.L. Ziebell et al. / Radiation Measurements 46 (2011) 1638e1642
pristine Bragg peak in a PMMA phantom at the LLUMC proton therapy facility. Monte Carlo GEANT4 simulations have demonstrated that a long the central axis of a proton beam the contribution of neutrons to the field, and subsequent diode response to neutrons, is negligible. The simulated response of the diode to protons is relatively constant along the plateau region of the Bragg peak with a decrease in response of 5% at a depth corresponding to half the range of the protons, and a further decrease of 15% in the vicinity of the Bragg peak (Poder, 2010). At a WED of 17.5 cm a was determined for each diode and recorded. This depth was chosen to best represent the proton energies expected during the out-of-field measurements. Measurements have demonstrated that each diode is approximately 10 times more sensitive to neutrons than protons per unit absorbed dose in Lucite. 3.2. Out-of-field measurements For the three stated measurement positions, Fig. 2 presents the absorbed dose to Lucite per 1 Gy absorbed dose to the SOBP as measured by the ionization chamber, and as derived for protons and neutrons separately using equations (2) and (3). Separation of the absorbed dose contributions from protons and neutrons shows that at 2.5 cm from the field edge, the absorbed dose deposited to the Lucite is almost entirely due to the deposition of energy by protons. This is expected as close to the field edge the radiation field primarily consists of protons scattered from the primary beam. At 12.5 cm from the field edge the absorbed dose deposited to Lucite by protons is two times less than the absorbed dose deposited to Lucite by neutrons either scattered into the phantom from beam modification devices or generated within the phantom material itself. At this depth protons scattered from the primary field do not necessarily have sufficient energy to travel 12.5 cm and so the absorbed dose deposited by protons is less than the absorbed dose deposited by neutrons. This is also seen at 22.5 cm. Fig. 3 presents the partial contributions to the absorbed dose to Lucite from protons and neutrons as obtained through the simulated GEANT4 study and compares these results with those obtained experimentally. The GEANT4 simulated results show the partial contribution to the absorbed dose in Lucite from protons is almost 1 next to the field edge. The experimentally derived partial contributions to the absorbed dose from protons and neutrons reached parity at a lateral distance of about 10 cm from the field edge, the GEANT4 results show parity at a similar distance. At lateral distances greater than 10 cm the partial contribution to the absorbed dose from neutrons exceeds that from protons. The simulated partial contribution from neutrons reaches a maximum at 40 cm, and then begins to fall, due to the contribution to the absorbed dose from high energy protons scattered directly from the nozzle of the machine entering the phantom at lateral distances greater than 40 cm. The experimentally derived partial contributions of protons and neutrons to the absorbed dose show the same tendency as simulated, however at 22.5 cm from the field edge the partial contribution to the absorbed dose from neutrons is higher than the contribution from protons, but there is not as big a difference as predicted by the GEANT4 simulation. 3.3. Review of method The presented results support the validity of the proposed method for separating the proton and neutron contributions to the absorbed dose deposited in out-of-field regions in proton therapy. An advantage of this method is the high spatial resolution achievable with diodes. Uncertainty in this method is mostly determined by uncertainties in the measured sensitivities of the diode to protons and
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neutrons, a and b. Since the displacement KERMA of a particle in Si is energy dependent, the measured sensitivity of the diode to both protons and neutrons depends on the energy spectrum of the particle the diode is exposed to during calibration. A mismatch of energy spectrums between calibration and the out-of-field measurements can introduce an uncertainty of more than 15% in b and 15e20% in a, as described above. In addition, the measured sensitivity of the diodes to neutrons via the aforementioned approach introduces uncertainty due to the ionization chamber measuring the contribution of photons to the absorbed dose. To reduce the uncertainty in b, future calibration should be performed in the neutron field downstream of the Bragg peak. GEANT4 studies have shown that the neutron spectrum in this region closely matches the neutron spectra at positions lateral to the field edge, and there will be no photon contribution to the absorbed dose measured by the ionization chamber. Due to the low fluence of particles in out-of-field regions, irradiation times to achieve a measurable voltage shift at positions lateral to the field edge was significant and required a dose of around 300 Gy be delivered to the SOBP. This added to the uncertainty in the measurement of DVF due to possible fading in the diodes. By using diodes with a longer base the sensitivity of the diodes to NIEL can be increased (Anokhin et al., 2009). A possible source of discrepancy between the experimental and GEANT4 simulated results is the difference in the WED of the two lateral series of measurements, 19 cm and 22.3 cm respectively. At a WED of 22.3 cm the average energy of scattered protons is less than the average energy of scattered protons at the same lateral distance from the field edge at a WED of 19 cm. This leads to a faster reduction in the partial dose contribution from protons with increasing lateral distance, as can be seen in Fig. 3. 4. Conclusion A novel approach to separating the proton and neutron contributions to the absorbed dose deposited at out-of-field regions in proton therapy using a Si PIN diode and a standard clinical ionization chamber has been presented. This method exploits the sensitivity of the diode to NIEL in silicon. Experimental separation of the proton and neutron contributions to the absorbed dose at positions lateral to a typical prostate therapy treatment field was successfully performed and showed reasonable agreement with a comparable GEANT4 simulation, taking into account uncertainty. The small size of the diodes makes them suitable for measurements close to the field edge, and in vivo in confined body cavities. Since the diode is at least 10 times more sensitive to neutrons than protons, the response of the diode alone can be used to quickly approximate the absorbed dose deposited by neutrons at lateral distances of more than 15e20 cm from the field edge, possibly close to a critical organ of interest. Further improvement of the method is required for reducing the uncertainties described above. References Anokhin, I., Zinets, O., Rosenfeld, A., Lerch, M., Yudelev, M., Perevertaylo, V., Reinhard, M., Petasecca, M., 2009. Studies of the characteristics of silicon neutron sensors. IEEE Trans. Nucl. Sci. 5 (6), 2290e2293. Brenner, D.J., Hall, E.J., 2008. Secondary neutrons in clinical proton radiotherapy: a charged issue. Med. Phys. 86 (2), 165e170. Carolan, M., Rosenfeld, A., 2006. A method for measuring tissue-equivalent dose using a PIN diode and activation foil in epithermal neutron beams with EN < 100 keV. Radiat. Prot. Dosim. 120, 487e490. Clasie, B., Wroe, A., Kooy, H., Depauw, N., Flanz, J., Paganetti, H., Rosenfeld, A., 2010. Assessment of out-of-field absorbed dose and equivalent dose in proton fields. Radiat. Prot. Dosim. 37, 311e321. Hall, E.J., 2006. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int. J. Radiat. Oncol. Biol. Phys. 65, 1e7.
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ICRP, 2003. Relative Biological Effectiveness (RBE), Quality Factor (Q), and Radiation Weighting Factor (WR). In: ICRP Publication, vol. 92 Ann. ICRP 33(4). ICRU Report 36, 1983. Microdosimetry. International Commission on Radiation Units and Measurements, Marylands. Poder, J., 2010. The Characterisation of Planar Silicon PIN Diodes for Use in Proton Therapy. Master Thesis. University of Wollongong. Rosenfeld, A.B., Anokhin, I.E., Barabash, L.I., Zinets, P.G., Litovchenko, V.I., Belovodsky, L.F., Dumik, A.I., Fominych, V.I., Petrov, V.I., Sluchenkov, G.F., Koval, G.N., 1990. PeIeN diodes with a wide measurement range of fast neutron doses. Radiat. Prot. Dosim. 33, 175e178. Rosenfeld, A.B., Kaplan, G., Carolan, M., Allen, B., Anokhin, I., Zinets, O., Khivrich, V., Litovchenko, P.G., 1999. Application of PeIeN diodes and Mosfets for dosimetry in Gamma and neutron radiation fields. Radiat. Prot. Dosim. 84, 349e352. Simpson, E., 2011. Private Communication. Smith, Alfred R., 2009. Vision 20/20: proton therapy. Med. Phys. 36, 556e568. Swartz, J.M., Thurston, M.O., 1965. Analysis of the effect of fast-neutron bombardment on the current-voltage characteristic of a conductivity-modulated peien diode. J. Appl. Phys. 37, 745e755.
Vasilescu, A., (INPE Bucharest), Lindstroem, G., (University of Hamburg), 2000. Displacement Damage in Silicon, On-line Compilation. http://sesam.desy.de/ members/gunnar/Si-dfuncs.html. Wroe, A., Rosenfeld, A., Schulte, R., 2007. Out-of-field dose equivalents delivered by proton therapy of prostate cancer. Med. Phys. 34 (9), 3449e3456. Wroe, A., Clasie, B., Kooy, H., Flanz, J., Schulte, R., Rosenfeld, A., 2009. Out-of-field dose equivalents delivered by passively scattered therapeutic proton beams for clinically relevant field configurations. Int. J. Radiat. Oncol. Biol. Phys. 73, 306e313. Xu, X.G., Bednarz, B., Paganetti, H., 2008. A review of dosimetry studies on externalbeam radiation treatment with respect to second cancer induction. Phys. Med. Biol. 53, 193e241. Yan, X., Titt, U., Koehler, A.M., Newhauser, M.D., 2002. Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field. Nucl. Instrum. Methods Phys. Res. A 478, 429e434. Yudelev, M., Alyousef, K., Brandon, J., Perevertailo, V., Lerch, M.L.F., Rosenfeld, A.B., 2004. Application of semiconductors for dosimetry of fast-neutron therapy beam. Radiat. Prot. Dosim. 110, 573e578.
Contents lists available at ScienceDirect
Radiation Measurements journal homepage: www.elsevier.com/locate/radmeas
Solid state diode e Ionization chamber method for measuring out-of-field neutron dose in proton therapy A.L. Ziebell a, *, B. Clasie c, A. Wroe d, R.W. Schulte d, M.I. Reinhard b, S.J. Dowdell a, M.L. Lerch a, M. Petasecca a, V.L. Perevertaylo e, O.S. Zinets f, I.E. Anokhin f, A.B. Rosenfeld a a
Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia Australian Nuclear Science and Technology Organisation, Lucas Heights, Sydney, Australia Massachusetts General Hospital and Harvard Medical School, Boston, USA d Loma Linda University Medical Center, Loma Linda, USA e SPA BIT, Ukraine f Institute for Nuclear Research, Kiev, Ukraine b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 November 2010 Received in revised form 17 April 2011 Accepted 7 May 2011
In proton therapy neutrons are introduced to out-of-field regions inside the patient. Clinicians would like to know the absorbed dose being deposited by neutrons separately to that from protons, so as to be able to directly apply their own dose equivalent weighting factors based on their opinion of the biological risk posed by neutrons in this region. The purpose of this study is to investigate a novel approach to experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions. The method pairs specially designed silicon PIN diodes with a standard clinical ionization chamber. The sensitivity of the Si diode to non-ionizing energy losses in silicon is exploited, and can be quantified by measuring the shift in forward voltage for a fixed injection current, pre and post irradiation. The mathematical relations that describe the response of the diode and the ionization chamber can be solved simultaneously to give the contributions to the absorbed dose from protons and neutrons separately. Experimental measurements were made at the Loma Linda University Medical Center (LLUMC), Loma Linda, and Massachusetts General Hospital (MGH), Boston, proton therapy facilities. Experimental separation of the partial proton and neutron contributions to the absorbed dose measured at positions lateral to a typical prostate therapy treatment field delivered to a Lucite phantom was successfully performed and compared with results from a GEANT4 simulation. The experimental results matched well with simulation confirming the validity and promise of the novel approach. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Out-of-field dosimetry Silicon diode Proton therapy Neutron dose
1. Introduction Proton therapy represents a major advance in radiation therapy (Smith, 2009). Unlike photons, protons deliver a maximum absorbed dose to tissue at the end of their range. This peaked dose, the Bragg peak, allows for a highly conformal treatment to be delivered to the tumor volume while providing maximal sparing to healthy tissue distal to the target. To achieve uniform coverage of the tumor volume, passive scattering or active beam scanning methods may be used to deliver treatment to the patient. Passive scattering systems employ a number of beam modification devices. Inelastic proton interactions with beam modification devices result in the production of high energy neutrons, which may enter the patient.
* Corresponding author. Tel.: þ61 2 4221 4574. E-mail address: [email protected] (A.L. Ziebell). 1350-4487/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.radmeas.2011.05.022
Neutrons have a higher relative biological effectiveness (RBE) than both photons and high energy primary scattered protons due to the production of low energy protons in elastic scattering reactions with hydrogenous material, along with the production of other high LET secondaries. Neutrons may play an important role in the induction of second cancer following treatment. Dose equivalent measurements are a method of quantifying the biological risk posed by radiation in out-of-field regions of proton therapy (Yan et al., 2002; Hall, 2006; Wroe et al., 2007, 2009). When calculating dose equivalents, radiation protection weighting factors and quality factors recommended by the ICRP or ICRU (ICRP 92, 2003; ICRU 36, 1983) may be used, depending on the approach taken. Both these weighting factors scale an absorbed dose in Gy, to the dose equivalent in Sv. Most commonly, an average factor is applied to the absorbed dose deposited by all particles at the site of interest. Bonner spheres are capable of measuring the dose equivalent from neutrons only (Yan et al., 2002), but have a poor spatial
A.L. Ziebell et al. / Radiation Measurements 46 (2011) 1638e1642
resolution and are not suitable for measurements near the field edge. Currently recommended weighting factors for individual particles in proton therapy are discussed in the literature (Xu et al., 2008; Brenner and Hall, 2008). Energy-averaged neutron weighting factors are typically between 2 and 11 and possibly as high as 25 in low dose regions. Limited data from human exposure to neutrons makes accurate determination of the neutron RBE for clinical endpoints difficult (Brenner and Hall, 2008). To have a greater control on quantifying the risk posed by neutrons, clinicians would like to know the absorbed dose deposited by neutrons separately from that deposited by protons, and from there assign their own neutron specific weighting factors based on experience with patient treatments. This approach is becoming more desirable as our understanding of radiobiology in therapy increases. At present, experimentally separating the proton and neutron contributions to the absorbed dose in out-of-field regions is a challenging task. The absorbed dose deposited by protons produced in neutron elastic scattering reactions cannot be distinguished from the absorbed dose deposited by protons scattered from the primary beam. With Monte Carlo radiation transport codes such as the GEANT4 toolkit, individual particles can be tracked and the absorbed dose deposited by neutrons at outof-field positions can be recorded separately from that due to protons. Recently, a GEANT4 study was performed to obtain the partial proton and neutron contributions to the absorbed dose at out-of-field positions in a Lucite phantom for a typical prostate therapy treatment delivered using passive techniques (Clasie et al., 2010). Experimental verification of the partial proton and neutron contributions to the absorbed dose were not possible with any of the experimental techniques available. In this study a novel experimental approach to separating the proton and neutron contributions to the absorbed dose in mixed photon, proton and neutron fields is introduced. The approach pairs a specially designed silicon PIN diode with a standard clinical ionization chamber. The diode can be used to measure the effects of non-ionizing energy losses (NIEL) in silicon. Previously, such a diode has been paired with activation foils to verify Monte Carlo simulations in neutron fields (Carolan and Rosenfeld, 2006). In this work the suitability of the proposed paired dosimeter method to out-of-field dosimetry in proton therapy is discussed, and the method is used to separate the partial contributions of protons and neutrons to the absorbed dose at points along a series of measurements lateral to the field edge of a typical prostate therapy treatment delivered to a Lucite phantom using passive techniques. These experimental results are compared with results from the previously mentioned GEANT4 simulation by Clasie et al. (2010).
1639
displacement damage cross section (Vasilescu and Lindstroem, 2000), which has units of cm2keV/g; and depends on the spectral fluence of particle type i incident on the diode. The measured forward voltage shift is given by equation (1), where l is a diode specific constant related to the base length, resistivity and recombination properties of the diode (Swartz and Thurston, 1965; Rosenfeld et al., 1990), in units of V/Gy, Dmtrl,i is the absorbed dose in the phantom material when the detector is replaced by phantom material, in units of Gy and Fi,1Gy(mtrl)(E) is the spectral fluence normalized to the spectral fluence required to deposit an absorbed dose of 1 Gy in the phantom material, in units of cm2 Gy1. For a mixed radiation field, the total shift in forward voltage, DVF, is the sum of all DVF,i
DVF;i ¼ l$Dmtrl;i
X
KSi;i ðEÞ$Fi;1GyðmtrlÞ ðEÞ
(1)
From here on, DVF,i/Dmtrl,i will be referred to as the sensitivity of the diode to particles of type i. In Fig. 1 KSi,i(E)$FiE,1Gy(TE) is shown where KSi,i is as described above, and Fi,E,1Gy(TE) is the fluence of particle type i with energy E required to deposit 1 Gy in adipose tissue, for both protons and neutrons separately. It can be seen that for the energy range relevant to proton therapy, KSi,i(E)$Fi,E,1Gy(TE) for neutrons is 10e100 times greater than KSi,i(E)$Fi,E,1Gy(TE) for protons. Thus when operating in NIEL mode, the sensitivity of the diode to neutrons is expected to be 10e100 times the sensitivity of the diode to protons, for the same absorbed dose in tissue. A big advantage of using this diode in a mixed photon, proton and neutron field, is that the sensitivity of the diode to the same absorbed dose in Lucite from photons is three orders of magnitude less than the sensitivity of the diode to fast neutrons (Rosenfeld et al., 1999), thus the response of the diode in out-of-field regions in proton therapy will be mostly due to the induced displacement damage effects resulting from the fluence of protons and neutrons. 2.2. Separating the proton and neutron absorbed dose The response of the aforementioned diode and a standard clinical ionization chamber are described in equations (2) and (3) assuming a mixed proton-neutron field. Both are functions of the
2. Materials and methods 2.1. Radiation damage in Si diodes When silicon devices are exposed to a radiation field, nonionizing energy losses (NIEL) may occur that lead to atom displacements in the silicon bulk. These non-ionizing effects are quantified in terms of displacement KERMA: the kinetic energy imparted to the displaced atoms as a result of interaction with the incident particle. Deposition of displacement KERMA in the silicon diode produces a change in the resistivity of the diode base and alters the minority carrier lifetime, changing the electrical characteristics of the diode (Swartz and Thurston, 1965; Rosenfeld et al., 1990). As a result a shift in the forward voltage of the diode, DVF, is measured for the same current injected pre and post irradiation. In a mixed radiation field, the forward voltage shift of the diode due to a particle of type i with energy E is due to the displacement KERMA of that particle in Si, KSi,i(E), determined by the
Fig. 1. KSi,i(E)$Fi,E,1Gy(TE), the sensitivity of a given diode to a particle of interest, considering the fluence of particle type i with energy E required to deposit 1 Gy in adipose tissue, for both protons and neutrons separately. It can be seen that for the energy range of interest the sensitivity of the diode to neutrons is expected to be 10e100 times the sensitivity of the diode to protons, for the same absorbed dose in tissue.
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absorbed dose deposited in the material of interest by protons and neutrons respectively.
DVF ¼ aDp þ bDn
(2)
DIC ¼ Dp þ Dn
(3)
Here a and b are the sensitivities of the diode to protons and neutrons respectively. The units of both are V/Gy. DVF and DIC are the measured forward voltage shift of the diode, and the absorbed dose in the phantom material as measured by the ionization chamber (IC), at the same point of interest. Dp and Dn are the respective proton and neutron deposited absorbed doses at this point. This expression for DIC does not explicitly include photon dose, which will of course be a component in any experimental DIC measurement using the ion chamber, but the photon component of the absorbed dose has been found to be negligible in out-of-field regions in passively delivered treatments (Clasie et al., 2010). Solving equations (2) and (3) provides separate analytical expressions for the neutron and proton absorbed doses in the material, Dp and Dn, in terms of the measurable quantities DVF, a, b and DIC. 2.3. Tissue equivalency of the Si diode GEANT4 simulations have shown that for out-of-field regions, neutrons of energy 0.15e20 MeV dominate the neutron fluence spectrum (Simpson, 2011). In this energy range, Si diodes operated as per the method described above are suitable for dosimetry applications due to the ratio of displacement KERMA in Si to neutron KERMA in tissue being approximately constant within 15%. Further, these diodes have been successfully used for tissue equivalent neutron dosimetry in fast neutron therapy (FNT) where the average energy of the neutron spectrum, 20 MeV, is similar to that found in out-of-field regions in proton therapy (Yudelev et al., 2004). 2.4. Experimental setup Experiments were carried out at the Loma Linda University Medical Center (LLUMC) and the Massachusetts General Hospital (MGH) proton therapy facilities. The diodes were ion implanted bulk PIN diodes with a base length of approximately 1 mm and pþ and nþ cross sections equal to 1.2 mm2. Each diode was housed in a Lucite probe of dimensions 50 28 200 mm3. All out-of-field measurements were performed at the Francis H. Burr Proton Therapy Center, MGH, for a typical passively scattered prostate therapy treatment delivered into a Lucite phantom. The range of the proton beam was 28 cm in water, with an 8 cm modulation and a 3.8 cm radius circular field size. The diodes were placed within the phantom at distances of 2.5, 12.5 and 22.5 cm lateral to the field edge, all at a water equivalent depth (WED) of 19 cm. After the diodes were irradiated they were removed and an Extradin T1 miniature Shonka thimble ionization chamber with 0.056 cm3 sensitive volume (SV), also housed in a Lucite probe, was placed at the former position of each diode and the same treatment was delivered to the phantom. The reproducibility of treatment delivery at this facility is within 0.5%. Post measurement DVF and DIC were normalized to the dose deposited to the spread out Bragg peak (SOBP) during the measurement. The separation of the absorbed dose contributions from neutrons and protons was calculated by solving equations (2) and (3). Results are presented in Fig. 2 and compared with the results from the GEANT4 Monte Carlo simulation by Clasie et al. (2010) in Fig. 3. In the simulation a similar proton therapy treatment was delivered to a Lucite phantom, and tracking was activated for protons, neutrons, electrons and
Fig. 2. The absorbed dose to Lucite per 1 Gy absorbed dose to the SOBP as measured by the ionization chamber, and as derived for protons and neutrons separately using equations (2) and (3).
photons. Voxels for recording the dose were located at different lateral distances from the field edge, at a WED of 22.3 cm. More details on this simulation can be found in (Clasie et al., 2010). 3. Results and discussion 3.1. Response of the Si diodes to neutrons and protons The sensitivity of each diode to neutrons, b, was measured by exposing the diodes to a neutron field obtained by delivering a 205 MeV proton beam into a 6.5 cm thick brass block which attenuated all protons. The diodes were each housed within their Lucite probe and the probes were placed between two 5 cm thick polystyrene blocks. The center of the diodes was a distance of 30.5 cm from the end of the brass beam block. The measured sensitivity of each diode was recorded. Calibration of the diodes in terms of a was performed along the central axis of a 225 MeV
Fig. 3. The partial contribution to the absorbed dose to Lucite from protons and neutrons as obtained through the simulated GEANT4 study and as experimentally derived using equations (2) and (3).
A.L. Ziebell et al. / Radiation Measurements 46 (2011) 1638e1642
pristine Bragg peak in a PMMA phantom at the LLUMC proton therapy facility. Monte Carlo GEANT4 simulations have demonstrated that a long the central axis of a proton beam the contribution of neutrons to the field, and subsequent diode response to neutrons, is negligible. The simulated response of the diode to protons is relatively constant along the plateau region of the Bragg peak with a decrease in response of 5% at a depth corresponding to half the range of the protons, and a further decrease of 15% in the vicinity of the Bragg peak (Poder, 2010). At a WED of 17.5 cm a was determined for each diode and recorded. This depth was chosen to best represent the proton energies expected during the out-of-field measurements. Measurements have demonstrated that each diode is approximately 10 times more sensitive to neutrons than protons per unit absorbed dose in Lucite. 3.2. Out-of-field measurements For the three stated measurement positions, Fig. 2 presents the absorbed dose to Lucite per 1 Gy absorbed dose to the SOBP as measured by the ionization chamber, and as derived for protons and neutrons separately using equations (2) and (3). Separation of the absorbed dose contributions from protons and neutrons shows that at 2.5 cm from the field edge, the absorbed dose deposited to the Lucite is almost entirely due to the deposition of energy by protons. This is expected as close to the field edge the radiation field primarily consists of protons scattered from the primary beam. At 12.5 cm from the field edge the absorbed dose deposited to Lucite by protons is two times less than the absorbed dose deposited to Lucite by neutrons either scattered into the phantom from beam modification devices or generated within the phantom material itself. At this depth protons scattered from the primary field do not necessarily have sufficient energy to travel 12.5 cm and so the absorbed dose deposited by protons is less than the absorbed dose deposited by neutrons. This is also seen at 22.5 cm. Fig. 3 presents the partial contributions to the absorbed dose to Lucite from protons and neutrons as obtained through the simulated GEANT4 study and compares these results with those obtained experimentally. The GEANT4 simulated results show the partial contribution to the absorbed dose in Lucite from protons is almost 1 next to the field edge. The experimentally derived partial contributions to the absorbed dose from protons and neutrons reached parity at a lateral distance of about 10 cm from the field edge, the GEANT4 results show parity at a similar distance. At lateral distances greater than 10 cm the partial contribution to the absorbed dose from neutrons exceeds that from protons. The simulated partial contribution from neutrons reaches a maximum at 40 cm, and then begins to fall, due to the contribution to the absorbed dose from high energy protons scattered directly from the nozzle of the machine entering the phantom at lateral distances greater than 40 cm. The experimentally derived partial contributions of protons and neutrons to the absorbed dose show the same tendency as simulated, however at 22.5 cm from the field edge the partial contribution to the absorbed dose from neutrons is higher than the contribution from protons, but there is not as big a difference as predicted by the GEANT4 simulation. 3.3. Review of method The presented results support the validity of the proposed method for separating the proton and neutron contributions to the absorbed dose deposited in out-of-field regions in proton therapy. An advantage of this method is the high spatial resolution achievable with diodes. Uncertainty in this method is mostly determined by uncertainties in the measured sensitivities of the diode to protons and
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neutrons, a and b. Since the displacement KERMA of a particle in Si is energy dependent, the measured sensitivity of the diode to both protons and neutrons depends on the energy spectrum of the particle the diode is exposed to during calibration. A mismatch of energy spectrums between calibration and the out-of-field measurements can introduce an uncertainty of more than 15% in b and 15e20% in a, as described above. In addition, the measured sensitivity of the diodes to neutrons via the aforementioned approach introduces uncertainty due to the ionization chamber measuring the contribution of photons to the absorbed dose. To reduce the uncertainty in b, future calibration should be performed in the neutron field downstream of the Bragg peak. GEANT4 studies have shown that the neutron spectrum in this region closely matches the neutron spectra at positions lateral to the field edge, and there will be no photon contribution to the absorbed dose measured by the ionization chamber. Due to the low fluence of particles in out-of-field regions, irradiation times to achieve a measurable voltage shift at positions lateral to the field edge was significant and required a dose of around 300 Gy be delivered to the SOBP. This added to the uncertainty in the measurement of DVF due to possible fading in the diodes. By using diodes with a longer base the sensitivity of the diodes to NIEL can be increased (Anokhin et al., 2009). A possible source of discrepancy between the experimental and GEANT4 simulated results is the difference in the WED of the two lateral series of measurements, 19 cm and 22.3 cm respectively. At a WED of 22.3 cm the average energy of scattered protons is less than the average energy of scattered protons at the same lateral distance from the field edge at a WED of 19 cm. This leads to a faster reduction in the partial dose contribution from protons with increasing lateral distance, as can be seen in Fig. 3. 4. Conclusion A novel approach to separating the proton and neutron contributions to the absorbed dose deposited at out-of-field regions in proton therapy using a Si PIN diode and a standard clinical ionization chamber has been presented. This method exploits the sensitivity of the diode to NIEL in silicon. Experimental separation of the proton and neutron contributions to the absorbed dose at positions lateral to a typical prostate therapy treatment field was successfully performed and showed reasonable agreement with a comparable GEANT4 simulation, taking into account uncertainty. The small size of the diodes makes them suitable for measurements close to the field edge, and in vivo in confined body cavities. Since the diode is at least 10 times more sensitive to neutrons than protons, the response of the diode alone can be used to quickly approximate the absorbed dose deposited by neutrons at lateral distances of more than 15e20 cm from the field edge, possibly close to a critical organ of interest. Further improvement of the method is required for reducing the uncertainties described above. References Anokhin, I., Zinets, O., Rosenfeld, A., Lerch, M., Yudelev, M., Perevertaylo, V., Reinhard, M., Petasecca, M., 2009. Studies of the characteristics of silicon neutron sensors. IEEE Trans. Nucl. Sci. 5 (6), 2290e2293. Brenner, D.J., Hall, E.J., 2008. Secondary neutrons in clinical proton radiotherapy: a charged issue. Med. Phys. 86 (2), 165e170. Carolan, M., Rosenfeld, A., 2006. A method for measuring tissue-equivalent dose using a PIN diode and activation foil in epithermal neutron beams with EN < 100 keV. Radiat. Prot. Dosim. 120, 487e490. Clasie, B., Wroe, A., Kooy, H., Depauw, N., Flanz, J., Paganetti, H., Rosenfeld, A., 2010. Assessment of out-of-field absorbed dose and equivalent dose in proton fields. Radiat. Prot. Dosim. 37, 311e321. Hall, E.J., 2006. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int. J. Radiat. Oncol. Biol. Phys. 65, 1e7.
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