- Email: [email protected]
157 YTTERBIUM SOURCES FOR BRACHYTHERAPY
S73 developing a novel rotational proton delivery device based on a linear accelerator called TULIP - TUrning LInac for Proton therapy. This new treatment device will be significantly reduced in size and costs compared to the synchrotron based treatment units available. Moreover, since TULIP is based on a linear accelerator with a pulse repetition rate in the range of 20-120Hz, energy variation times will be in the order of a few milliseconds depending on the repetition rate. In order to evaluate achievable dose distributions with TULIP we have developed a C-based computer software simulating the respective dynamic delivery process. As input data the software uses plan data for a static spot-scanning delivery of protons from 110 different beam directions covering up to 330° rotation of the gantry with an angular spacing of the individual beams of 3°. This plan data was derived by the inhouse treatment planning software “KonRad” [Nill 2004] of the German Cancer Research Center (DKFZ). The beam spots are delivered starting from the most distal spot for each beam direction. The individual delivery time of each spot depends on the chosen pulse repetition rate of the linear accelerator. Gantry rotation is modelled by rotation of the target voxel positions during the delivery of the beam spots. An additional couch motion can be modelled by simulating a shift of the patient in the plane perpendicular to the gantry rotation plane. All dynamic parameters can be varied by user input in order to find the most beneficial set of treatment parameters for the target to be irradiated. The resulting dose distributions were evaluated by Dose Volume Histograms (DVH) comprising minimum doses to 99% (D99%), 95% (D95%) and 1% (D1%) of the target volume as listed in table 1. For this study a circular slice water phantom with a slice thickness of 1mm and a diameter of 5cm has been chosen as well as a cylindrical water phantom with a target diameter of 2.65cm and a length of 3cm. Different combinations of pulse repetition rates (16Hz, 100Hz) and gantry rotation velocities (6°/s, 9°/s) were tested. For the circular water phantom dynamic dose delivery with repetition rates higher than 16Hz in combination with a gantry speed of 6°/s resulted in dose distributions comparable to the statically delivered dose distributions. Static dose delivery resulted to D99% and D1% values of 57.1Gy and 62.5Gy respectively. Dynamic delivery with a pulse repetition rate of 16Hz in combination with a gantry rotation velocity of 6°/s lead to a minimum dose of 57.7Gy to 99% of the target volume. A pulse repetition rate of 100Hz in combination with 6°/s gantry velocity resulted in a minimum dose of 57.3Gy to 99% of the target volume. Minimal doses to 1% of the volume were found to be 62.0Gy for 16Hz and 62.4Gy for 100Hz respectively. An increased gantry speed of 9°/s with the same pulse repetition rate of 16Hz resulted in a distorted dose distribution manifested in a reduced minimum dose of 27.2Gy to 99% of the volume and 62.6Gy to 1% of the tumour volume. Furthermore, we observed a reduction of the minimum dose to 50% of the volume by 5.4Gy compared to the statically delivered dose. For a cylindrical target additional couch motion in the range of 0.1mm/s perpendicular to the gantry rotation plane lead to comparable dosimetric effects as for the circular water phantom with the same dynamic parameters. Our study shows that rotational dynamic
ICTR-PHE 2012 delivery of protons is feasible and can lead to conformal dose distributions comparable to those gained by static delivery with spot-scanning for a suitable set of treatment parameters. In the future, we would like to extend our studies to moving organs and take advantage of the very short pulse delivery time of this novel treatment device. Pulse repetition rate [Hz]
Gantry velocity [°/s]
D99% [Gy]
D95% [Gy]
D50% [Gy]
D1% [Gy]
0
0
57.1
58.0
59.9
62.5
16
6
57.7
58.5
59.9
62.0
100
6
57.3
58.1
59.9
62.4
16
9
27.2
33.3
54.5
62.6
Table 1: Minimal doses to 99%, 95%, 50% and 1% of the target volume for different combinations of treatment parameters. [Pedroni 1995] Pedroni E, Bacher R, Blattmann H, Böhringer T, Coray A, Lomax A, Lin S, Munkel G, Scheib S and Schneider U 1995 The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization Med. Phys 22 37-53 [Nill 2004] Nill S, Bortfeld T, Oelfke U 2004 Inverse planning of intensity modulated proton therapy Z. Med. Phys. 14 35-40 157 YTTERBIUM SOURCES FOR BRACHYTHERAPY S. Akulinichev, V. Derzhiev, L. Kravchuk INR of RAS, Moscow, Russia The isotope Yb-169 is known as a perspective material for radioactive sources for High Dose Rate (HDR) Brachytherapy of malignant tumors. Its average photon emission energy is 93 KeV and the half-life 32 days. Compared to other isotopes for HDR brachytherapy, iridium and cobalt, this isotope has asignificantly lower emission energy and requires a much lighter shielding. The activity and the clinical properties of standard-size ytterbium sources are comparable with iridium sources, but the medical application of ytterbium sources is much more convenient and cheep. The physical properties of Yb-169 allow to use this isotope in the Low Dose Rate Brachytherapy as well, competing with conventional iodine sources. However, the ytterbium sources are still a rare exotics for radiologists, partially due to the lack of standard technology of the source production. We have developed an original laser technology of the production of primary isotope Yb-168 enriched up to the 20% concentration (the view of the laser system is presented below). It is important that this technology requires much less electrical power than standard electromagnetic technology, used for the Yb-168 production in other institutions. We then worked out standard-size titanium capsules with Yb-168 and activated these sources by reactor neutrons. An original nanotechnology was developed in order to get a sufficient density of ytterbium inside the capsules. The measured activity of these ytterbium sources was about 6 Ci. This activity is typical for HDR brachytherapy
S74 sources. As a conclusion, we have developed a full chain of original and relatively cheep technology of the production of new promising radioactive sources with Yb-169 for brachytherapy.
158 DIFFUSION-WEIGHTED MRI FOR EARLY TUMOR RESPONSE ASSESSMENT DURING TREATMENT V. Vandecaveye Department of Radiology, University Hospitals Leuven, Belgium In biological tissue, water molecule displacements occur within and between three major compartments: the intracellular space (IS), the extravascular extracellular space (EES) and the intravascular space (IVS). In solid malignant lesions, the EES will be relatively diminished compared to the IS, due to an increased number of cells, cellular pleomorphism, large cell volume and neo-angiogenic vessels disorganized in a chaotic structure. This increased microstructural density will lead to a restriction of the random water molecule movement. Contrary, the EES will be relatively enlarged compared to the IS in tissues with low cell density such as in inflammation, due to the presence of interstitial oedema, and in necrosis, due to the absence of any organized tissue structures. leading to a facilitation of random water molecule movement. Diffusion-weighted magnetic resonance imaging (DWI), is made susceptible to the differences in water mobility by two equally large but opposite gradients. The first gradient induces a phase dispersion of water molecules second gradient pulse rephases the water molecules. For static water molecules, the effects of both gradients will cancel each other out, and the measured signal intensity (SI) should be identical to the one measured without any diffusion-sensitizing gradients. However, biological tissue, the rephasing will always be incomplete in biological tissues, resulting in a net signal loss dependent on the amount and speed of the movement, and on the amount of diffusion-sensitization of the gradients. In order to provide an overview of the movements present in the tissue, several DWI measurements need to be acquired with different diffusion-sensitization. In most clinical examinations, consecutive DW images with increasing b-values ranging from 0 to 1000 s/mm2 are acquired. By repeating the sequence with different b-values, the signal decay with increasing b-value can be quantified using the apparent diffusion coefficient (ADC). If a graph is made plotting the b-values relative to the
ICTR-PHE 2012 measured signals at the respective b-value, a curve fitting can be performed from which the ADC can be deduced. Hypercellular tissue, characterized by a limited EES and diffusion restriction, will only show limited signal decay with increasing b-value (more complete rephasing due to limited water mobility) with a persistent high SI on the native DWI images with high b-value (eg, 1000 s/mm2) resulting in a low ADC. On the contrary, areas of low cellularity, showing a large EES and facilitation of water movement, will show rapid signal decay with increasing b-value (incomplete rephasing due to pronounced water mobility) with low or absent SI on the native DWI images with high b-value (eg, 1000 s/mm2) resulting in a high ADC. As such, a combination of high SI at high b-value images and low ADC could differentiate malignant from benign tissue, or in case of treatment follow-up, from necrosis or inflammation. The potential value of DWI lies in its insensitivity to inflammatory changes, making the technique highly robust for treatment assessment early during or after treatment. Predictive imaging prior to or during radiation treatment of HNC is gaining more and more interest. The ability to predict later tumour response may aid in the proper initiation or adaptation of non-surgical treatment and help to plan systemic and/or radiation treatment (neo-adjuvant treatment and definitive concomitant CRT) on an individual basis, aiming to improve treatment efficiency and decrease of toxic side effects. The potential value of DWI lies in its insensitivity to inflammatory changes, making the technique highly robust for treatment assessment early during or after treatment. For predictive imaging during chemoradiotherapy (CRT), 2 seperate studies - respectively by Kim et al and Vandecaveye et al - in 40 respectively 30 patients have shown that ADC-changes (ΔADC) relative to baseline, 1week or 2 weeks and 4 weeks during CRT are predictive for treatment outcome (complete remission versus tumour recurrence). As reference standard, 6 month patient follow-up and histopathology and 2 year patient follow-up were used. Sensitivities ranged from 86% to 100% and specificities from 83% to 96% and in the study of Vandecaveye et al, the change in ADC was shown to be an independent predictor of 2-year locoregional control. These findings have already been confirmed in a follow-up study by King et al. Pivotal to the further clinical development of DWI as a predictive diagnostic tool is the inclusion image evaluation that include the spatial distribution of response in order to safely guide escalated radiation doses to non-responding tumour components and thus potentially help RT-planning. Currently, software is being developed that is able to depict the spatial distribution of tumour response on DWI and thus visually separate responding from non-responding tumour components. 160 STEREOTACTIC ABLATIVE RADIOTHERAPY REDUCES THE INVASIVE CAPACITY OF CANCERASSOCIATED FIBROBLASTS ISOLATED FROM HUMAN LUNG TUMOURS T. Hellevik1, I. Pettersen2, J.O. Winberg2, V. Berg2, R.H. Paulssen2, K. Bartnes1, L.T. Busund1,2, 1,2 2 R. Bremnes , I. Martinez-Zubiaurre 1 University Hospital of Northern Norway
ICTR-PHE 2012 delivery of protons is feasible and can lead to conformal dose distributions comparable to those gained by static delivery with spot-scanning for a suitable set of treatment parameters. In the future, we would like to extend our studies to moving organs and take advantage of the very short pulse delivery time of this novel treatment device. Pulse repetition rate [Hz]
Gantry velocity [°/s]
D99% [Gy]
D95% [Gy]
D50% [Gy]
D1% [Gy]
0
0
57.1
58.0
59.9
62.5
16
6
57.7
58.5
59.9
62.0
100
6
57.3
58.1
59.9
62.4
16
9
27.2
33.3
54.5
62.6
Table 1: Minimal doses to 99%, 95%, 50% and 1% of the target volume for different combinations of treatment parameters. [Pedroni 1995] Pedroni E, Bacher R, Blattmann H, Böhringer T, Coray A, Lomax A, Lin S, Munkel G, Scheib S and Schneider U 1995 The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization Med. Phys 22 37-53 [Nill 2004] Nill S, Bortfeld T, Oelfke U 2004 Inverse planning of intensity modulated proton therapy Z. Med. Phys. 14 35-40 157 YTTERBIUM SOURCES FOR BRACHYTHERAPY S. Akulinichev, V. Derzhiev, L. Kravchuk INR of RAS, Moscow, Russia The isotope Yb-169 is known as a perspective material for radioactive sources for High Dose Rate (HDR) Brachytherapy of malignant tumors. Its average photon emission energy is 93 KeV and the half-life 32 days. Compared to other isotopes for HDR brachytherapy, iridium and cobalt, this isotope has asignificantly lower emission energy and requires a much lighter shielding. The activity and the clinical properties of standard-size ytterbium sources are comparable with iridium sources, but the medical application of ytterbium sources is much more convenient and cheep. The physical properties of Yb-169 allow to use this isotope in the Low Dose Rate Brachytherapy as well, competing with conventional iodine sources. However, the ytterbium sources are still a rare exotics for radiologists, partially due to the lack of standard technology of the source production. We have developed an original laser technology of the production of primary isotope Yb-168 enriched up to the 20% concentration (the view of the laser system is presented below). It is important that this technology requires much less electrical power than standard electromagnetic technology, used for the Yb-168 production in other institutions. We then worked out standard-size titanium capsules with Yb-168 and activated these sources by reactor neutrons. An original nanotechnology was developed in order to get a sufficient density of ytterbium inside the capsules. The measured activity of these ytterbium sources was about 6 Ci. This activity is typical for HDR brachytherapy
S74 sources. As a conclusion, we have developed a full chain of original and relatively cheep technology of the production of new promising radioactive sources with Yb-169 for brachytherapy.
158 DIFFUSION-WEIGHTED MRI FOR EARLY TUMOR RESPONSE ASSESSMENT DURING TREATMENT V. Vandecaveye Department of Radiology, University Hospitals Leuven, Belgium In biological tissue, water molecule displacements occur within and between three major compartments: the intracellular space (IS), the extravascular extracellular space (EES) and the intravascular space (IVS). In solid malignant lesions, the EES will be relatively diminished compared to the IS, due to an increased number of cells, cellular pleomorphism, large cell volume and neo-angiogenic vessels disorganized in a chaotic structure. This increased microstructural density will lead to a restriction of the random water molecule movement. Contrary, the EES will be relatively enlarged compared to the IS in tissues with low cell density such as in inflammation, due to the presence of interstitial oedema, and in necrosis, due to the absence of any organized tissue structures. leading to a facilitation of random water molecule movement. Diffusion-weighted magnetic resonance imaging (DWI), is made susceptible to the differences in water mobility by two equally large but opposite gradients. The first gradient induces a phase dispersion of water molecules second gradient pulse rephases the water molecules. For static water molecules, the effects of both gradients will cancel each other out, and the measured signal intensity (SI) should be identical to the one measured without any diffusion-sensitizing gradients. However, biological tissue, the rephasing will always be incomplete in biological tissues, resulting in a net signal loss dependent on the amount and speed of the movement, and on the amount of diffusion-sensitization of the gradients. In order to provide an overview of the movements present in the tissue, several DWI measurements need to be acquired with different diffusion-sensitization. In most clinical examinations, consecutive DW images with increasing b-values ranging from 0 to 1000 s/mm2 are acquired. By repeating the sequence with different b-values, the signal decay with increasing b-value can be quantified using the apparent diffusion coefficient (ADC). If a graph is made plotting the b-values relative to the
ICTR-PHE 2012 measured signals at the respective b-value, a curve fitting can be performed from which the ADC can be deduced. Hypercellular tissue, characterized by a limited EES and diffusion restriction, will only show limited signal decay with increasing b-value (more complete rephasing due to limited water mobility) with a persistent high SI on the native DWI images with high b-value (eg, 1000 s/mm2) resulting in a low ADC. On the contrary, areas of low cellularity, showing a large EES and facilitation of water movement, will show rapid signal decay with increasing b-value (incomplete rephasing due to pronounced water mobility) with low or absent SI on the native DWI images with high b-value (eg, 1000 s/mm2) resulting in a high ADC. As such, a combination of high SI at high b-value images and low ADC could differentiate malignant from benign tissue, or in case of treatment follow-up, from necrosis or inflammation. The potential value of DWI lies in its insensitivity to inflammatory changes, making the technique highly robust for treatment assessment early during or after treatment. Predictive imaging prior to or during radiation treatment of HNC is gaining more and more interest. The ability to predict later tumour response may aid in the proper initiation or adaptation of non-surgical treatment and help to plan systemic and/or radiation treatment (neo-adjuvant treatment and definitive concomitant CRT) on an individual basis, aiming to improve treatment efficiency and decrease of toxic side effects. The potential value of DWI lies in its insensitivity to inflammatory changes, making the technique highly robust for treatment assessment early during or after treatment. For predictive imaging during chemoradiotherapy (CRT), 2 seperate studies - respectively by Kim et al and Vandecaveye et al - in 40 respectively 30 patients have shown that ADC-changes (ΔADC) relative to baseline, 1week or 2 weeks and 4 weeks during CRT are predictive for treatment outcome (complete remission versus tumour recurrence). As reference standard, 6 month patient follow-up and histopathology and 2 year patient follow-up were used. Sensitivities ranged from 86% to 100% and specificities from 83% to 96% and in the study of Vandecaveye et al, the change in ADC was shown to be an independent predictor of 2-year locoregional control. These findings have already been confirmed in a follow-up study by King et al. Pivotal to the further clinical development of DWI as a predictive diagnostic tool is the inclusion image evaluation that include the spatial distribution of response in order to safely guide escalated radiation doses to non-responding tumour components and thus potentially help RT-planning. Currently, software is being developed that is able to depict the spatial distribution of tumour response on DWI and thus visually separate responding from non-responding tumour components. 160 STEREOTACTIC ABLATIVE RADIOTHERAPY REDUCES THE INVASIVE CAPACITY OF CANCERASSOCIATED FIBROBLASTS ISOLATED FROM HUMAN LUNG TUMOURS T. Hellevik1, I. Pettersen2, J.O. Winberg2, V. Berg2, R.H. Paulssen2, K. Bartnes1, L.T. Busund1,2, 1,2 2 R. Bremnes , I. Martinez-Zubiaurre 1 University Hospital of Northern Norway