The effect of the removal of Flattening filter on beam characteristics " (Flattening Filter" ) . 8 .

) . 8 . Introduction: Even though new methods are in use or under development to treat cancer, radiotherapy using linear accelerators (linacs) is still the most frequently used treatment technique for this purpose. During last two decades, several developments have been introduced on the linac such as intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), Stereotactic Body Radiotherapy (SBRT) and others. The main purpose of these techniques is to deliver a high dose to tumour and low dose to normal tissues as much as possible (Meyer et al. 2007). However, by using conventional linear accelerators (linacs), several problems limit the ability of these techniques to obtain the optimum result of the overall treatment course. These problems arise from the relatively low dose rate of conventional linacs, the high neutron contamination level when they are operated at energies higher than 8 MeV and the quite high out-of-field dose. One way to compensate these problems is to remove the flattening filter from the head of linac or what is known as flattening filter free mode (FFF) (Kry et al 2008, Vassiliev et al 2006, Georg et al 2011). The main purpose of the project is to study the effect of removal flattening filter from medical linacs on FFF beam characteristics and trying to improve these parameters.

Characteristics of FFF beam

Dose rate The greatest benefit of removing the FF is to increase the linac dose rate thus reducing the beam-on time which can translate into a reduction in delivery time in a number of treatment cases such as SBRT lung cancer and respiratory gating in treatments required an organ motion control (Vassiliev et al 2006, Wang et al 2011). Several studies reported that the dose rate in FFF mode for Varian and Electa linacs is about 2, 2.5 and 5 times higher for 6, 10 and 18 MV beams, respectively (Vassiliev et al 2006, Cashmore 2008, Kragl et al 2009, Dalaryd et al 2010). To my knowledge, no one has assessed the 12 and 15 MV photon beams of Varian and Electa linacs and the only study done on a 15MV photon beam was for Siemens linac (Chofor et al 2011,2102). The biological effect of increasing the dose rate was studied

by Lohse et al (2011). They examined the change in cancer cell survival (in vitro) with different dose rates per pulse using FF and FFF beams. They found that the higher the dose rate, the lesser the cell survival will be. However, this study used only two types of brain cancer cell lines (the glioblastoma multiforme T98G and the glioblastoma astrocytoma U87MG) and therefore more studies on other types of cancer cells and normal cells as well are required in order to have a better understanding of the effect of changing the dose rate. Beam profile Removing the FF, as mentioned before, affects the linac beam uniformity. However, this is not a problem nowadays since new techniques have been introduced such as IMRT which can compensate for this effect by adapting the multi-leaf collimators (MLCs) during the treatment course can adjust the fluence distribution inside the beam field to compensate this effect. Besides, the flattened beam produces only a uniform dose distribution inside a homogenous phantom and therefore, a flattened beam does not provide an advantage in a realistic case. In addition, the beam profile of the unflattened beam has less variation with depth in the homogenous phantom compared with a flattened beam as seen in figure 3.1 (Vassiliev et al 2006, Titt et al 2006).

Figure Error! No text of specified style in document..1: The variation in beam profile with depth for 1010 cm2 6 MV FF and FFF beams (Vassiliev et al 2006).

Out-of-field dose Another advantage of removing the FF is the reduction of the out-of-field dose which reduces the probability to induce secondary cancers. Diallo et al 2009 have reported that about 66% of secondary cancers occur at the edge of the treatment field and 22% at a distance > 5 cm from the treatment field. This reduction of out-of-field dose is a result of the reduction in the number of photons scattered from the linac head. Dalaryd et al (2010) calculated the ratio of scattered photons from the linac head using Monte Carlo (MC) simulation and they stated that the scattered ratio was reduced by 31.70.3% and 47.60.5% for 6 MV and 10 MV

beams, respectively. However, another study by Kry et al (2010) reported that the reduction in out-of-field dose is not always achievable and it depends on the patient and treatment parameters. Kry et al (2010) studied the out-of-field dose from a 6 MV FFF beam and they divided the out-of-field region into three regions. The first region was located at <3 cm from the field edge and the dose reduced in this region due to the reduction in the linac head scattering. The second region was located between 3-15 cm from the field edge and the dose increased in this region due to the increase in the patient scattering. The last region was located 15 cm from the field edge and the dose decreased in this region due to the reduction in head leakage. They also concluded that the FFF plays a role when the treatment field sizes are less than 44 cm2 and therefore the optimal effect from FFF will be only for stereotactic treatment (Kry et al 2010). X-ray Spectra The effect of removing FF on X-ray spectra has been examined by several authors using MC calculations. The X-ray spectrum of FFF beam was found softer than the FF beam and that has the effect on the penetration of the beam inside the patient and therefore in order to get the same penetration as the FF beam the energy of the incident electron beam should increase (Georg et al 2011). Another result of softening the beam is increasing the surface dose to the patient which needs further investigation. However, there is an advantage of softer X-ray spectra in case of a portal imaging. Tyner et al (2009) examined the change in the response of the electronic portal imaging device (EPID) of unflattened beams. They found that the sensitivity of the EPID increased and the measured profile had minimum change with increasing phantom thickness. Additionally, the shape of X-ray spectra of FFF beam does not have as much dependency on the position inside the field-size as the FF beam. Figure 3.2 shows the difference between the shape of X-ray spectra of FF and FFF beam of a 6 MV linac at the isocentre and at the edge of the field-size (Dalaryd et al 2010).

Figure Error! No text of specified style in document..2 Photon Spectra at central axis and at field edge (dashed line) of 4040 cm2 field-size for FF (a) and FFF (b) of a 6MV beam (Dalaryd et al 2010).

Depth dose The change in the photon spectrum and the mean energy of FFF beam has an effect on the depth dose at the central axis. The percentage depth dose (PDD) curves of FFF beams show a faster fall-off after the depth at maximum dose (dmax) compared to the FF ones (figure 3.3) and they were found to be equivalent to those of FF beams with lower energies. For example, the PDD after dmax of the 6MV FFF beam was found to be similar to the 4 MV FF beam. Similarly, the PDD after dmax of the 18MV FFF beam was found to be similar to the 15 MV FF beam (Vassiliev et al 2006, Georg et al 2011, Tsiamas et al 2011).

Figure Error! No text of specified style in document..3: the PDD curves of the 6MV FF (dashed) and FFF beams (solid) and the 4 MV FF beam (filled circles) for a 1010 cm2 field-size (Vassiliev et al 2006).

Electron contamination Another disadvantage of the FFF is the higher electron level inside the beam which leads to potential risk to produce high surface dose (Titt et al 2006). Mesbahi (2008) reported that the electron fluence for unflattened 18MV beam is about 1.6 times higher than that for the flattened one. To reduce this effect, a number of studies have been examined inserting a thin plate in place of the FF in order to reduce the surface dose at the patient plane but it needs further investigation (Georg et al 2011). Neutron production Flattening filters are made of medium and/or high Z materials which firstly, increase the head scatter that increase the photoneutron production from other head components1 (i.e. primary collimators, jaws and MLCs) and secondly, can produce a noticeable photoneutrons (in the case of high Z materials are used). Several studies have investigated the effect of removing the flattening filter on photoneutron production (Mesbahi 2009, Mesbahi& Nejad 2008, Kry et al 2007&2008). Kry et al (2007) used gold activation to measure the neutron fluence for 18

See section 2.3

MeV FFF beam of a Varian linac. They found that the neutron fluence was reduced by a factor of 69%. Mesbahi (2009) used MC calculation to study the effect of FFF on Elekta SL25 linac. He found results very close to those obtained for a Varian linac. This reduction results in a decrease in the number of photons created in the target required to produce the same dose at the isocentre as well as the decrease in the head scatter. To my knowledge, no one has studied the effect of removing FF on neutron production from the FFF linac beam with energy different from 18 MV except Chofor et al (2011) who calculated the difference in photoneutron strength for a 15 MV FF and FFF Siemens Primus linac) and the effect of field-size of FFF linacs on neutron production has not been studied in detail even for a 18 MV FFF beam.

The effect of adding a plate in place of the FF on ionisation chamber response and beam characteristics
A flattening filter produces large amounts of secondary electrons used to generate a positiondependent dose in the ionization chamber to control the beam. When the flattening filter is removed, the amount of secondary electrons decreases and may not generate a detectable signal in the ionization chamber (Chashmore 2008). Alternatively, removing the flattening filter allows part of the primary electrons to penetrate the target and reaches the patient plane and that could cause an increase the surface dose (Titt et al 2006). The higher surface dose for a FFF beam arises also from the softer X-ray spectra compared with those for a FF beam, as mentioned before. Several studies have investigated the effect of adding different plates in place of the FF in order to reduce the surface dose and to increase the signal in the ionization chamber. Cashmore (2008) examined the effect of 1.1 mm Al and 1.9 mm Cu plates for Elekta 6MV photon beam on the electron level and the response of the ionisation chamber. Both plates increased the signal of the ionization chamber but the reduction in the surface dose was not achieved. Titt et al (2006) used MC methods to study the effect of 11 mm nylon and 2 mm copper plates on electron and photon fluences for a 6 MV Varian photon beam. The electron fluence decreases by a factor of 2.7 and 3.1 for nylon and copper plates but it still 48% and 28% higher compared to the FF beam, respectively. The photon fluence was found 40% and 37% higher than that for a FF beam for nylon and copper, respectively. Similarly, a 1mm steel plate was used in a Varian 2300C linac by Stathakis et al (2009) on both photon modes 6 MV and 18 MV. Thicker plates have also been examined by several authors. 6 mm copper was used in studies on Elekta linacs (Kragle et al 2009, Tyner et al 2009). OBrian et al (1991) used 13 mm aluminium plate underneath the target. The thicker plates have the advantage in safety aspects if any failure occurs in the target (Georg et al 2011). However, more investigations in the plate thickness and composition are required in order to obtain the optimum result in the ion

chamber response, out-of-field dose and surface dose. Additionally, the effect of the plate on neutron production and out-of field doses has not been examined.

Project Plan The objective of the project is to investigate the effect of removing the flattening filter from medical linacs on the dosimetric properties of the beam in order to improve the overall treatment outcome. In order to achieve the objective six steps should be investigated:

1. Studying the effect of removing the Flattening filter for different linac energies from different linacs (Varian and Electa). 2. Examining the effect of adding a plate made of different materials and has different thicknesses on the production of photoneutron, the out-of-field dose, the surface dose and the ionisation chamber response. 3. Doing several measurements at the King Khalid University Hospital on linacs operating with and without FF in order to assess our MC simulations. 4. Studying the effect of field-sizes of the unflattened beam on the photoneutron production. 5. Simulating the treatment room of the FFF linac to quantify the effect of removal the FF on neutron fluences and neutron dose-equivalents at different locations inside and outside the treatment room. 6. Studying (in vitro) different types of cancer cells and normal cells as well in order to have a better understanding of the effect of changing the dose rate on the cell survival ratio. References Cashmore, J. 2008, "The characterization of unflattened photon beams from a 6 MV linear accelerator", Physics in Medicine and Biology, vol. 53, pp. 1933. Chofor, N., Harder, D., Willborn, K., Rhmann, A. & Poppe, B. 2011, "A direction-selective flattening filter for clinical photon beams. Monte Carlo evaluation of a new concept", Physics in Medicine and Biology, vol. 56, pp. 4355.

Chofor, N., Harder, D., Willborn, K.C. & Poppe, B. 2012, "Internal scatter, the unavoidable major component of the peripheral dose in photon-beam radiotherapy", Physics in Medicine and Biology, vol. 57, pp. 1733.

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Lohse, I., Lang, S., Hrbacek, J., Scheidegger, S., Bodis, S., Macedo, N.S., Feng, J., Ltolf, U.M. & Zaugg, K. 2011, "Effect of high dose per pulse flattening filter-free beams on cancer cell survival", Radiotherapy and Oncology, . Mesbahi, A. 2009, "A Monte Carlo study on neutron and electron contamination of an unflattened 18-MV photon beam", Applied Radiation and Isotopes, vol. 67, no. 1, pp. 55-60. Mesbahi, A. & Nejad, F.S. 2008, "Monte Carlo study on a flattening filter-free 18-MV photon beam of a medical linear accelerator", Radiation Medicine, vol. 26, no. 6, pp. 331-336. Meyer, J.L., Verhey, L., Xia, P. & Wong, J. 2007, "New technologies in the radiotherapy clinic", Imrt, Igrt, Sbrt: Advances in the Treatment Planning and Delivery of Radiotherapy, vol. 40, pp. 1-17. Stathakis, S., Esquivel, C., Gutierrez, A., Buckey, C.R. & Papanikolaou, N. 2009, "Treatment planning and delivery of IMRT using 6 and 18 MV photon beams without flattening filter", Applied Radiation and Isotopes, vol. 67, no. 9, pp. 1629-1637. Titt, U., Vassiliev, O., Pnisch, F., Dong, L., Liu, H. & Mohan, R. 2006, "A flattening filter free photon treatment concept evaluation with Monte Carlo", Medical Physics, vol. 33, pp. 1595. Tyner, E., McClean, B., McCavana, P. & af Wetterstedt, S. 2009, "Experimental investigation of the response of an a-Si EPID to an unflattened photon beam from an Elekta Precise linear accelerator", Medical Physics, vol. 36, pp. 1318. Vassiliev, O.N., Titt, U., Pnisch, F., Kry, S.F., Mohan, R. & Gillin, M.T. 2006, "Dosimetric properties of photon beams from a flattening filter free clinical accelerator", Physics in Medicine and Biology, vol. 51, pp. 1907. Wang, Y., Khan, M.K., Ting, J.Y. & Easterling, S.B. 2012, "Surface Dose Investigation of the Flattening Filter-Free Photon Beams", International Journal of Radiation Oncology* Biology* Physics, .