Today, I will present the second of the two lectures on neutron interactions. 1
The main goal of this lecture is to tell you a little about clinical neutron therapy, first with fast neutron beams, and then with boron neutron capture. Then we ll discuss contamination neutrons in radiation therapy, both in conventional photon therapy and in proton therapy. Then, we ll talk a little bit about neutron shielding for radiation therapy and some of the things that we consider, especially in the door design. Finally, we ll talk a bit about neutron dose. There are really two big things when we think about neutron dose. There is neutron dose in a high-dose situation, in other words, dose to the patient, and how we calculate that in a clinical facility. And then there is neutron protection, which deals with low-dose quantities. These two subjects are handled are entirely differently from each other. 2
The first half of today s lecture will focus on neutron radiotherapy. I will discuss two types of therapy including fast neutron therapy and boron neutron capture therapy. Then I will briefly provide some details about the history of neutron therapy and current facilities and the types of tumors that have been successfully treated with neutrons. 3
For most hospital facilities the neutron sources will come from cyclotrons, either from accelerating deuterons or protons and impinging them on a beryllium target. Note that unlike the production of photon beams, in which the accelerated particles impinge on a high-z target, to produce neutron beam the accelerated particles impinge on a low-z target. Now, to have a beam that has a high enough energy to penetrate into tissue of the patient and not cause extreme skin reactions, you need to have those deuterons and protons with energies of at least 50 MeV. And historically neutrons got a really bad rap, because a lot of the early accelerators were low energy, 16 MeV and 26 MeV, and so those beams were not really penetrating very deeply into tissue, and neither the dosimetry nor the radiation biology was very well understood. So the doses they were giving the patients were not very well controlled. In the new facilities, of which there are only actually 3 in the United States, the accelerating potential is greater than 50 MeV. 4
When designing a neutron therapy facility, the decision whether to use protons or deuterons to generate a fast neutron beam is greatly affected by the amount of space available for the facility because accelerating deuterons require a cyclotron that is approximately twice the size of a cyclotron to accelerate protons because the mass of a deuteron is twice that of a proton. Such a large cyclotron is impractical for a hospital and would more likely be found at a research facility. 5
The first method of generating a fast neutron beam is a stripping process. In this method, deuterons are accelerated to a high energy (>50 MeV) and then impinge on a beryllium-9 target. The deuteron collides with the beryllium target and a proton is stripped from the deuteron and added to the beryllium nucleus, converting it to boron-10. The recoil neutron from the proton-stripped deuteron retains some of the incident kinetic energy of the accelerated deuteron. Some gamma rays are also produced as well. 6
This figure shows two neutron spectra resulting from deuteron bombardment of Beryllium. The spectrum on the left is from an older accelerator with deuterons accelerated to 16 MeV, whereas the spectrum on the right is from a newer accelerator in which deuterons are accelerated to 50 MeV. In both spectra there is a single peak, with a modal value of approximately 40% of the energy of the incident deuterons. 7
The second method of generating a fast neutron beam is a knock-out process. In this method, protons are accelerated to a high energy, >50 MeV, and then impinged on a beryllium-9 target. The protons knock out neutrons, and for each one of the knocked-out neutrons, you end up with a boron-9 atom. Let us consider an example with a single proton impinging a single beryllium-9 atom. The proton collides with the beryllium-9 target. The proton is added to the beryllium-9 nucleus and a neutron is knocked-out of to the beryllium nucleus, converting it to a boron-9 nucleus. The neutron retains some of the kinetic energy of the incident proton. 8
This figure shows two neutron spectra resulting from proton bombardment of beryllium. The dashed line is an unfiltered spectrum that was produced from protons accelerated to 43 MeV. This spectrum spans a wide range of energies from zero up to the energy of the incident protons. The low-energy neutrons in this spectrum are not penetrating enough for therapy and would cause severe skin reaction. These low-energy neutrons must thus be filtered-out. This figure is from the Hall textbook, which says that a low-z material such as polyethylene was used to filter the beam. Polyethylene contains a long chain of hydrocarbons, consequently, there is a large amount of hydrogen to remove the low-energy component. Recall from the previous lecture that elastic scatter dominates for lower energy fast neutrons and that nuclei with lower mass are more effective on a per collision basis for slowing down neutrons. So, a low-z material like polyethylene would reduce the energy of these neutrons to thermal energies. But, just using polyethylene might just make the problem worse because the beam would have even more low-energy neutrons. However, if the polyethylene were doped with a material like boron, which has a high thermal neutron cross section, it would effectively remove the thermalized neutrons from the beam achieving an overall harder spectrum as is shown by the solid line. Consequently, it is very likely that boronated polyethylene was used to filter the beam. 9
6 MV is the most commonly used beam energy in photon radiation therapy and thus provides a good frame of reference. The d max for a 6-MV photon beam is 1.5 cm and percent depth dose at 10 cm is approximately 65%. This figure compares isodoses for a fast neutron beam and a 6-MV photon beam. Here, we see that isodose values 70% are very similar for the two beams. However, isodose lines less than 70% are at more shallow depths for neutrons than for photons, resulting in a somewhat steeper fall-off in dose. 10
If we compare a neutron beam to a 6-MV photon beam, we observe differences in the machine design. For example, an accelerator that produces photon beams uses high-z materials such as lead or tungsten to collimate the beam. These materials are easily accommodated within the treatment gantry by a target-to-isocenter distance of 100 cm. However, neutron beams require a greater distance between the target and isocenter to accommodate thicker collimators. 11
Neutron beams are typically collimated with several different materials designed to remove neutrons. The neutrons are first slowed down with hydrogen-rich materials such as polyethylene. Then an absorbing material is used to remove the thermal neutrons. This is usually followed by a high Z-material to absorb the γ-ray photons that are a byproduct of activation that follows absorption. Because of the large size of the collimator, we use longer treatment distances for neutron therapy, closer to 140 cm. In some facilities, in order to achieve these long distances, the floor of the treatment room actually opens up and the table drops down beneath the floor. 12
The first clinical experiences with fast neutron beams were at the Lawrence Berkeley Laboratory in California and at the Hammersmith Hospital in London. We are not going to discuss these experiences in detail, but if you are interested, you can find more details in a radiobiology text such as the Eric Hall textbook, Radiobiology for the Radiologist. 13
Currently, there are three neutron therapy facilities in the United States. One facility is the Northern Illinois University Institute for Neutron Therapy at Fermilab. This is an older facility and it s at a research laboratory. Patients at this facility are treated in a sitting position, and there is a beam port that comes out of the wall, which is more like a research beam line. Two newer institutions are at the University of Washington Medical Center and the Gershenson Radiation Oncology Center in Detroit. 14
Here is some information about the University of Washington and Gershenson facilities, which are both relatively new. The University of Washington Medical Center uses a cyclotron to accelerate protons. They have a rotating gantry and multileaf collimator in their facility. The Gershenson facility at Wayne State University in Detroit uses a superconducting cyclotron to accelerate deuterons. This is a smaller standard cyclotron, or at least that is what it says on their website. They also have a rotating gantry and are equipped with a multileaf collimator. 15
There is evidence that certain subgroups of patients may benefit from neutron therapy compared to high-energy photon therapy. Specifically, neutrons have been shown to be effective for patients with slower growing tumors such as adenoidcystic carcinoma (cancer of parotid glands), locally advanced prostate cancer, locally advanced head and neck tumors, inoperable sarcomas, and cancer of the salivary glands. Slower growing tumors are generally considered to be late responding than early responding tumors. The effectiveness of neutrons for these types of cancer is likely related to the higher LET of neutrons. Remember the dose from neutrons is actually delivered by high-energy charged particles set in motion following interactions between neutrons and nuclei in the tissue. In your radiation biology class you learned (or will learn) that high-let radiation is more likely to result in double strand breaks whereas low-let photons are more likely to result in single strand breaks. Further discussion of this topic is beyond the scope of this course and is covered in the radiation biology course. 16
In addition to the information in Chapter 24 of the Eric Hall textbook, Radiobiology for the Radiologist, you may also find the following references of interest. I will not expect you to read these, it is just a list for those who are particularly interested in the topic. 17
Let s switch topics and discuss boron neutron capture therapy (BNCT). BNCT uses a neutron beam that interacts with boron injected into a patient. BNCT depends on the interaction of slow neutrons with boron-10 to produce alpha particles and lithium nuclei. The idea behind BNCT is that you preferentially deliver boron to a tumor or a target site that you want to irradiate. Patients are given an intravenous injection of a boron-10 tagged chemical that preferentially binds to tumor cells. The boron has a high cross section for interaction with thermal neutrons, 3837 barns. When the boron absorbs the thermal neutrons you get the reaction between the boron and the neutron. The boron-10 absorbs the thermal energy neutron and ejects a 1.47 MeV short-range alpha particle and 0.84 MeV lithium ion which deposit most of their energy within the cell containing the original boron-10 atom. So if you can infuse the boron into the tumor cell and then put the radiation in, you get the alpha particles out, delivering dose in a region very close to the site of the initial interaction. Thus the dose to your normal tissue is going to be very small; in an ideal situation, you don t have a lot of the boron compound in the normal tissue and the alpha particles are going to deliver the dose quite locally to the tumor. It is a very elegant idea. Some of the complications, however, have been in determining the right boron compound and the preferential absorption of the boron compound between tumor and normal cells. 18
In the previous lecture, we saw that there were several nuclei with high thermal absorption cross sections. So, why do we use boron over some of these other nuclei such as cadmium-113, which has a cross section that is five times greater than boron-10? First, boron-10 is non-radioactive and readily available, comprising approximately 20% of naturally occurring boron. Second, the emitted particles (α and 7 Li) have high LET, and their combined path lengths are approximately one cell diameter; i.e., about 12 microns. Theoretically, this limits the deposition of radiation dose to those tumor cells that have taken up a sufficient amount of 10 B, and simultaneously sparing normal cells. Finally, the chemistry of boron is well understood and allows it to be readily incorporated into a multitude of different chemical structures. 19
An important consideration for BNCT is that thermal neutrons are not very penetrating and external irradiation with thermal neutrons would really only be effective for very shallow tumors. Therefore in reality, the patient is irradiated with epithermal neutrons, which are thermalized within the superficial tissues via elastic scatter collisions with hydrogen. While this improves the penetration compared to thermal neutrons and reduces the skin dose, the peak doses are still somewhat shallow, typically occurring at 2 to 3 cm. 20
This slide is a schematic of the boron-10 interaction s involved in BNCT. As I indicated previously, we use an epithermal neutron beam, rather than a thermal neutron beam. The epithermal beam loses energy by elastically scattering with hydrogen in tissue. 21
The neutrons become thermalized and are captured by the boron-10 nuclei. These boron-10 nuclei become boron-11 nuclei in a short-lived excited state. 22
The boron-11 nuclei then split into alpha particles, lithium-7 nuclei, and gamma rays. 23
Sweet and colleagues first demonstrated in 1952 that certain boron compounds would concentrate in human brain tumor relative to normal brain tissue. Shortly thereafter, clinical trials were initiated at Brookhaven National Laboratory and at MIT. Unfortunately, these trials failed to show any evidence of therapeutic efficacy. It became clear later that there were two major reasons for their lack of success. First the study used thermal neutrons, which were insufficiently penetrating and second the boron compounds that were used in the trials were freely diffusible and did not achieve selective localization in the tumor. Later, more encouraging results were observed in clinical studies done in Japan for the treatment of malignant gliomas and melanoma. At present, there are several groups in the U.S. and abroad working on BNCT for melanoma and gliomas. 24
The first part of today s lecture dealt with the direct use of neutrons in radiation therapy. The second half of today s lecture will switch gears from therapy and focus on the production of secondary neutrons, that is, contamination neutrons in radiation therapy. 25
We find contamination neutrons produced both in x-ray therapy as well as in proton therapy. Contamination neutrons in x-ray therapy result from (γ,n) reactions with high atomic number materials in the head of the linac. We learned about these interactions in our unit on photon interactions with matter. The neutrons come out of the head of the linac and move around essentially isotropically. They can go anywhere in the patient and not just to the target site. So we are thinking about irradiation of distant organs and the induction of secondary cancers to distant organs. We can nicely control the photons so we do not deliver dose to the liver or kidneys when treating the prostate, for example. Because we can t control the direction of the neutron dose, neutron contamination is a serious area of interest in terms of induction of secondary cancers, especially for younger patients. 26
Contamination neutrons in proton therapy result from (p,n) reactions with high-z materials in the nozzle, but can also be the result of (p,n) reactions within the patient. Both (γ,n) and (p,n) reactions are threshold reactions. So why do we observe (p,n) and not observe (γ,n) reactions in the patient? It has to do with the energies of the photon and proton beams and the answer to this question should be clear by the end of today s lecture. 27
Let s first look at the (γ,n) reactions that we see in the head of a linear accelerator. 28
This plot is an example of a spectrum for an 18 MV photon beam. The maximum energy of the photon spectrum is determined by the energy of the electrons incident on the Bremsstrahlung target. In this example, the maximum energy of the electrons was 18 MeV. So, the photon beam has a range of energies from 0 to 18 MeV, with an average energy of approximately 6 MeV. Now, let s consider this spectrum in the context of (γ,n) reaction cross sections and threshold energies. 29
This plot, shows the (γ,n) reaction cross section for Pb-207 in black. Note that the threshold energy is slightly greater than 6 MeV and increases rapidly between 6 and about 18 MeV, and then begins to drop. So, in the context of the Bremsstrahlung spectrum on the previous slide, secondary neutrons can be generated from interactions between high-energy photons in that spectrum and Pb-207 in the head of the linear accelerator. Note that there is no production of neutrons from a 6-MV beam because the photon energy is less than the threshold for neutron production. A lot of times you will see in the medical physics literature that you do not need to consider neutron shielding for accelerators operating at energies below 10 MV. It is not that the threshold for neutron production is 10 MeV, but for a 10 MV beam, there will be almost no photons with energies above the threshold region. The (γ,n) reaction cross sections for other high-z materials in the linac head such as tungsten are similar to that of Pb-207. 30
Now let s compare the spectra for 18 MV and 15 MV photon beams. Notice that the 18 MV beam has more photons above the (γ,n) threshold and most are in the region where the (γ,n) cross section dramatically increases. So, how would we expect this to affect neutron contamination. We would expect to see substantially more contamination neutrons for an 18 MV beam compared to a 15 MV beam. And there is, in fact, a twofold increase observed in neutron dose for 18 MV beams compared to 15 MV beams. 31
Now, let s consider the reaction cross sections for nuclei in the human body. This is a plot of (γ,n) reaction cross sections for carbon, oxygen, and nitrogen. Nitrogen has the lowest threshold energy at about 8 MeV and carbon has the highest at about 19 MeV. These thresholds are much higher than those observed for high-z materials and there are very few photons in our 15 MV and 18 MV spectra above these thresholds. Also, the magnitude of the reaction cross-sections are an order of magnitude lower than those for high-z materials. Therefore, we can conclude that secondary neutron production is tissue is extremely unlikely and essentially negligible. 32
Now, let s look at the neutron spectra emanating from the head of the linear accelerator. We are making the photons from an electron beam. Those photons then hit the collimators, the primary jaws, the flattening filter and the target. And it s from (γ,n) interactions in the linac head that we are getting these secondary neutrons in the therapy beam. The initial distribution of secondary neutrons generated in the linac head from these (γ,n) reactions is approximately isotropic, and the energy distribution actually looks like a fission spectrum. 33
The neutron energy then decreases as a consequence of the neutron transport through the components of the treatment head (primary collimators, flattening filter, secondary jaws, MLC, etc). The primary mechanisms of energy loss in high-z materials in the linac head are inelastic scattering and (n,2n) reactions. 34
This figure from NCRP-79 compares a 252 Cf fission spectrum to a photoneutron spectrum for 15 MeV electrons striking a tungsten target (designated 15 MeV W PN bare). You can see that these two spectra are very similar. Also shown is the photoneutron spectrum with 10 cm of tungsten to simulate materials in the gantry head. Notice that the energy is decreased as a consequence of inelastic scatter and (n,2n) reactions. Also shown is a spectrum with 10 cm of tungsten shielding inside a concrete room to simulate materials in the gantry head in an actual treatment vault. The energy is further reduced from elastic scatter with low-z materials in the concrete. 35
This figure shows photoneutron spectra measured for a Varian linac operated at 3 different beam energies 15, 18, and 20 MV. Notice that qualitatively these spectra are similar, with fast neutron peaks centered at approximately 0.23 MeV and have similar average energies. Each spectrum also has a low-energy tail that arose from neutrons scattered throughout the treatment vault. The obvious distinction between the three spectra is the total neutron fluence per MU. A 1.7-fold increase in fluence was observed as the energy increased from 15 to 18 MV and a 1.4-fold increase was observed as energy was increased from 18 to 20 MV. 36
The other set of reactions that produce secondary neutrons that we might find of interest are the (p,n) reactions, which cause secondary neutron production in proton beams. 37
There are several significant differences between proton beams and x-ray beams that need to be taken into consideration when looking at the production of contamination neutrons. First of all, we need to look at the energy spectra of typical clinical proton beams. Clinical proton beams have a much smaller energy spread compared to photon beams, and the maximum energies of proton beams are considerably higher, typically in the range of 100 250 MeV. 38
This plot shows the (p,n) reaction cross section for Pb-207 in black. Note that the threshold energy is approximately 10 MeV and increases rapidly with energy. So, in the context of the energies used for clinical proton beam therapy, neutrons can be generated from interactions between high-energy protons in that spectrum and Pb-207 in the nozzle. Also, the magnitude of the (p,n) cross sections are an order of magnitude greater than the magnitude of the (γ,n) cross sections. The (p,n) reaction cross sections for other high-z materials in the linac head such as tungsten are similar to that of Pb-207. So the amount of contamination neutrons in a proton beam is going to be much greater than the neutron contamination in a photon beam. 39
Now, let s consider the reaction cross sections for nuclei in the human body. This is a plot of (p,n) reaction cross sections for carbon-12. The threshold is somewhat higher than that for Pb-207, but still well below the energy of a clinical proton beam. Therefore, we can conclude that in contrast to our observation that (γ,n) reactions in tissue are extremely unlikely for a clinical photon beam, (p,n) reactions in tissue can occur in a clinical proton beam, and this neutron contamination dose is not negligible. 40
These data are a plot of Monte Carlo simulated neutron spectra for clinical proton beams. These neutron spectra were generated via (p,n) reactions. Note that there are two pronounced peaks in all neutron spectra, joining each other at approximately 10 MeV. The low-energy peak is similar in shape for all proton energies, with neutron energies ranging from 0 to about 10 MeV, and having a modal energy of about 1 MeV. These low-energy neutrons are mainly produced from evaporation processes and are isotropically distributed. The high-energy neutron peak starts at about 10 MeV and extends up to the maximum proton energy, with the modal energy varying with the proton energy. The high-energy peak contains forward-peaked neutrons from direct (nucleon nucleon) reactions produced in intranuclear cascades and neutrons ejected from the compound-nucleus and pre-equilibrium processes. The major difference between secondary neutrons from proton and photon beams is the energy; neutrons from proton beams have much higher energy. This results from the much higher maximum energy of proton beams (~range: 100 MeV to 250 MeV) versus the maximum energy of photons (~ range: 10 MV to 25 MV) energy of the incident photon. 41
Finally, this slide gives you a set of references on neutrons. 42
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