Preclinical investigations towards the first spacer gel application in prostate cancer treatment during particle therapy at HIT

Radiation Oncology

Thomas Haberer³  Oliver Jäkel³  Katia Parodi³  Christoph Bert²  Jürgen Debus³  Klaus Herfarth³  Gregor Habl³  Daniel Unholtz³  Stephan Brons³  Patrick Campbell¹  Julia Bauer³  Antoni Ruciński³ 

[1]Augmenix Inc., Waltham, MA, USA

[2]Biophysics division, GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, Darmstadt, Germany

[3]Heidelberg Ion Beam Therapy Center and Department of Radiation Oncology, Heidelberg University Clinic, Im Neuenheimer Feld 400, Heidelberg, 69120, Germany

关键词: Spacer gel;    Prostate cancer;    Particle therapy;    Radiation therapy;   

Others  :  1153826
DOI  :  10.1186/1748-717X-8-134

 received in 2013-02-07, accepted in 2013-05-24,  发布年份 2013

【 摘 要 】

Background

The application of spacer gel represents a promising approach to reliably spare the rectal frontal wall during particle therapy (IJROBP 76:1251-1258, 2010). In order to qualify the spacer gel for the clinical use in particle therapy, a variety of measurements were performed in order to ensure the biological compatibility of the gel, its physical stability during and after the irradiation, and a proper definition of the gel in terms of the Hounsfield Unit (HU) values for the treatment planning system. The potential for the use of the spacer gel for particle therapy monitoring with off-line Positron Emission Tomography (PET) was also investigated.

Results

The spacer gel implanted to the prostate patient in direct neighbourhood to the clinical target volume does not interfere with the particle therapy treatment planning procedure applied at Heidelberg Ion Beam Therapy Centre (HIT). The performed measurements show that Bragg-peak position of the particles can be properly predicted on the basis of computed tomography imaging with the treatment planning system used at HIT (measured water equivalent path length of 1.011 ±0.011 (2σ), measured Hounsfield Unit of 28.9 ±6.1 (2σ)). The spacer gel samples remain physically unchanged after irradiation with a dose exceeding the therapeutic dose level. The independently measured Bragg-Peak position does not change within the time interval of 10 weeks.

Conclusions

As a result of the presented experiments, the first clinical application of spacer gel implant during prostate cancer treatment with carbon ions and protons was possible at HIT in 2012. The reported pre-clinical investigations demonstrate that use of spacer gel is safe in particle therapy in presence of therapy target motion and patient positioning induced particle range variations. The spacer gel injected between prostate and rectum enlarge the distance between both organs, which is expected to clinically significantly decrease the undesirable exposure of the most critical organ at risk, i.e. rectal frontal wall. Further research on the composition of spacer gel material might lead to additional clinical benefits by validation of particle therapy of prostate via post-therapeutic PET-imaging or by patient positioning based on the gel as a radio-opaque marker.

【 授权许可】

   
2013 Ruciński et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Dearnaley D, Hall E, Jackson C, Lawrence D, Huddart R, Eeles R, Gadd J, Warrington A, Bidmead M, Horwich A: Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer PSA control and side effects. Brit J Cancer 2005, 92(3):488-498.
• [2]Kuban D, Tucker S, Dong L, Starkschall G, Huang E, Cheung M, Lee A, Pollack A: Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008, 70(1):67-74.
• [3]Schardt D, Elsässer T, Schulz-Ertner D: Heavy-ion tumor therapy: Physical and radiobiological benefits. Rev Mod Phys 2010, 82:383-425.
• [4]Peschke P, Karger CP, Scholz M, Debus J, Huber PE: Relative biological effectiveness of carbon ions for local tumor control of a radioresistant prostate carcinoma in the rat. Int J Radiat Oncol Biol Phys 2011, 79:239-246. [http://www.sciencedirect.com/science/article/pii/S0360301610029500 webcite]
• [5]Beltran C, Herman MG, Davis BJ: Planning target margin calculations for prostate radiotherapy based on intrafraction and interfraction motion using four localization methods. Int J Radiat Oncol Biol Phys 2008, 70:289-295. [http://www.sciencedirect.com/science/article/pii/S0360301607039909 webcite]
• [6]Bylund KC, Bayouth JE, Smith MC, Hass AC, Bhatia SK, Buatti JM: Analysis of interfraction prostate motion using megavoltage cone beam computed tomography. Int J Radiat Oncol Biol Phys 2008, 72(3):949-956tt. [http://www.sciencedirect.com/science/article/pii/S036030160802974X webcite]
• [7]Ghilezan MJ, Jaffray DA, Siewerdsen JH, Herk MV, Shetty A, Sharpe MB, Jafri SZ, Vicini FA, Matter RC, Brabbins DS, Martinez AA: Prostate gland motion assessed with cine-magnetic resonance imaging (cine-MRI). Int J Radiat Oncol Biol Phys 2005, 62(2):406-417. [http://www.sciencedirect.com/science/article/pii/S0360301603022120 webcite]
• [8]Rietzel E, Bert C: Respiratory motion management in particle therapy. Med Phys 2010, 37(2):449-460. [http://link.aip.org/link/?MPH/37/449/1 webcite]
• [9]Kupelian PA, Thakkar VV, Khuntia D, Reddy CA, Klein EA, Mahadevan A: Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Long-term outcomes. Int J Radiat Oncol Biol Phys 2005, 63(5):1463-1468. [http://www.sciencedirect.com/science/article/pii/S0360301605009661 webcite]
• [10]Tsuji H, Yanagi T, Ishikawa H, Kamada T, etsu Mizoe J, Kanai T, Morita S, Tsujii H: Hypofractionated radiotherapy with carbon ion beams for prostate cancer. Int J Radiat Oncol Biol Phys 2005, 63(4):1153-1160. [http://www.sciencedirect.com/science/article/pii/S0360301605007091 webcite]
• [11]Pinkawa M, Corral NE, Caffaro M, Piroth MD, Holy R, Djukic V, Otto G, Schoth F, Eble MJ: Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer. Radiother Oncol 2011, 100(3):436-441. [http://www.sciencedirect.com/science/article/pii/S0167814011005317 webcite]. [Special Issue on Medical Physics and Brachytherapy]
• [12]Krämer M, Jäkel O, Haberer T, Kraft G, Schardt D, Weber U: Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization. Phys Med Biol 2000, 45(11):3299. [http://stacks.iop.org/0031-9155/45/i=11/a=313 webcite]
• [13]Schneider U, Pedroni E, Lomax A: The calibration of CT Hounsfield units for radiotherapy treatment planning. Phys Med Biol 1996, 41:111. [http://stacks.iop.org/0031-9155/41/i=1/a=009 webcite]
• [14]Rietzel E, Schardt D, Haberer T: Range accuracy in carbon ion treatment planning based on CT-calibration with real tissue samples. Radiat Oncol 2007, 2:14. [http://www.ro-journal.com/content/2/1/14 webcite] BioMed Central Full Text
• [15]Bauer J, Unholtz D, Sommerer F, Kurz C, Haberer T, Herfarth K, Welzel T, Combs S, Debus J, Parodi K: Implementation and initial clinical experience of offline PET/CT-based verification of scanned carbon ion treatment. Radiother Oncol 2012.
• [16]Paganetti H, Shih HA, Michaud S, Loeffler JS, DeLaney TF, Liebsch NJ, Munzenrider JE, Fischman AJ, Knopf A, Bortfeld T, Parodi K: Patient study of In Vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy. Int J Radiat Oncol Biol Phys 2007, 68(3):920-934. [http://www.sciencedirect.com/science/article/pii/S036030160700377X webcite]
• [17]Knopf A, Parodi K, Bortfeld T, Shih HA, Paganetti H: Systematic analysis of biological and physical limitations of proton beam range verification with offline PET/CT scans. Phys Med Biol 2009, 54(14):4477. [http://stacks.iop.org/0031-9155/54/i=14/a=008 webcite]
• [18]Jäkel O, Jacob C, Schardt D, Karger C, Hartmann G: Relation between carbon ion ranges and x-ray CT numbers. Med Phys 2001., 28(4)
• [19]Jakoby BW, Bercier Y, Conti M, Casey ME, Bendriem B, Townsend DW: Physical and clinical performance of the mCT time-of-flight PET/CT scanner. Phys Med Biol 2011, 56(8):2375. [http://stacks.iop.org/0031-9155/56/i=8/a=004 webcite]
• [20]Haberer T, Becher W, Schardt D, Kraft G: Magnetic scanning system for heavy ion therapy. Nucl Instrum Methods Phys Res Sect A: Accelerators, Spectrometers, Detectors Assoc Equip 1993, 330(1–2):296-305. [http://www.sciencedirect.com/science/article/pii/016890029391335K webcite]
• [21]Battistoni G, Muraro S, Sala P, Cerutti F, Ferrari A, Roesler S, Fassó A, Ranft J: The FLUKA code: Description and benchmarking. AIP Conf Proc 2007, 896:31-49.
• [22]Fassó A, Ferrari A, Ranft J, Sala P: FLUKA: a multi-particle transport code. Tech. rep., CERN-2005-10, INFN/TC_05/11, SLAC-R-773 2005
• [23]Parodi K, Ferrari A, Sommerer F, Paganetti H: Clinical CT-based calculations of dose and positron emitter distributions in proton therapy using the FLUKA Monte Carlo code. Phys Med Biol 2007, 52(12):3369. [http://stacks.iop.org/0031-9155/52/i=12/a=004 webcite]
• [24]Parodi K, Mairani A, Brons S, Hasch BG, Sommerer F, Naumann J, Haberer T, Debus J, Jäkel O: Monte Carlo simulations to support start-up and treatment planning of scanned proton and carbon ion therapy at a synchrotron-based facility. Phys Med Biol 2012, 57(12):3759. [http://stacks.iop.org/0031-9155/57/i=12/a=3759 webcite]
• [25]Pinkawa M, Piroth MD, Holy R, Escobar-Corral N, Caffaro M, Djukic V, Klotz J, EbleK MJ: Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall. Radiother Oncol 2013, 106(2):220-224. [http://www.sciencedirect.com/science/article/pii/S0167814012005294 webcite]
• [26]Bert C, Durante M: Motion in radiotherapy particle therapy. Phys Med Biol 2011, 56:113-144.