Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

Background: Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). Materials and methods: The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90Rectum), respectively. Results: The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. Conclusions: The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal exposure to high treatment dose and, therefore, can reduce the hazard of rectal toxicity in ion beam therapy of PC. The results of this study enable modifications of the PC ion therapy protocol such as dose escalation or hypofractionation

Prompt gamma spectroscopy for absolute range verification of 12C ions at synchroton-based facilities

[EN] The physical range uncertainty limits the exploitation of the full potential of charged particle therapy. In this work, we face this issue aiming to measure the absolute Bragg peak position in the target. We investigate p, He-4, C-12 and O-16 beams accelerated at the Heidelberg Ion-Beam Therapy Center. The residual range of the primary C-12 ions is correlated to the energy spectrum of the prompt gamma radiation. The prompt gamma spectroscopy method was demonstrated for proton beams accelerated by cyclotrons and is developed here for the first time for heavier ions accelerated by a synchrotron. We develop a detector system that includes (i) a spectroscopic unit based on cerium(III) bromide and bismuth germanium oxide scintillating crystals, (ii) a beam trigger based on an array of scintillating fibers and (iii) a data acquisition system based on a FlashADC. We test the system in two different scenarios. In the first series of experiments, we detect and identify 19 independent spectral lines over a wide gamma energy spectrum in the presence of the four ion species for different targets, including a water target with a titanium insert. In the second series of experiments, we introduce a collimator aiming to relate the spectral information to the range of the primary particles. We perform extensive measurements for a C-12 beam and demonstrate submillimetric precision for the measurement of its Bragg peak position in the experimental setup. The features of the energy and time spectra for gamma radiation induced by p, He-4 and O-16 are investigated upstream and downstream from the Bragg peak position. We conclude the analysis by extrapolating the required future developments, which would be needed to achieve range verification with a 2 mm accuracy during a single fraction delivery of D=2 Gy<i physical dose.The author R.D.B. is supported by the International Max Planck Research School for Quantum Dynamics in Physics, Chemistry and Biology, Heidelberg, Germany. P.M.M. is supported by a research fellowship for postdoctoral researchers from the Alexander von Humboldt Foundation, Bonn, Germany. The authors thank the Radiation Protection Department of the DKFZ, in particular Mechthild Kammer, for the support with calibration sources. The authors also thank the staff of the Department of Medical Physics in Radiation Oncology of the DKFZ, in particular Gernot Echner, Armin Runz and Peter Haring for the support with the experimental setup.Dal Bello, R.; Martins, PM.; Brons, S.; Hermann, G.; Kihm, T.; Seimetz, M.; Seco, J. (2020). Prompt gamma spectroscopy for absolute range verification of 12C ions at synchroton-based facilities. Physics in Medicine and Biology. 65(9):1-23. https://doi.org/10.1088/1361-6560/ab7973S123659Amaldi, U., & Kraft, G. (2005). Radiotherapy with beams of carbon ions. Reports on Progress in Physics, 68(8), 1861-1882. doi:10.1088/0034-4885/68/8/r04Aricò, G., Gehrke, T., Gallas, R., Mairani, A., Jäkel, O., & Martišíková, M. (2019). Investigation of single carbon ion fragmentation in water and PMMA for hadron therapy. Physics in Medicine & Biology, 64(5), 055018. doi:10.1088/1361-6560/aafa46Böhlen, T. T., Cerutti, F., Chin, M. P. W., Fassò, A., Ferrari, A., Ortega, P. G., … Vlachoudis, V. (2014). The FLUKA Code: Developments and Challenges for High Energy and Medical Applications. Nuclear Data Sheets, 120, 211-214. doi:10.1016/j.nds.2014.07.049Bragg, W. H., & Kleeman, R. (1905). XXXIX. On the α particles of radium, and their loss of range in passing through various atoms and molecules. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science, 10(57), 318-340. doi:10.1080/14786440509463378Brun, R., & Rademakers, F. (1997). ROOT — An object oriented data analysis framework. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 389(1-2), 81-86. doi:10.1016/s0168-9002(97)00048-xCastriconi, R., Ciocca, M., Mirandola, A., Sini, C., Broggi, S., Schwarz, M., … Russo, P. (2016). Dose–response of EBT3 radiochromic films to proton and carbon ion clinical beams. Physics in Medicine and Biology, 62(2), 377-393. doi:10.1088/1361-6560/aa5078Guttormsen, M., Tveter, T. ., Bergholt, L., Ingebretsen, F., & Rekstad, J. (1996). The unfolding of continuum γ-ray spectra. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 374(3), 371-376. doi:10.1016/0168-9002(96)00197-0Haberer, T., Debus, J., Eickhoff, H., Jäkel, O., Schulz-Ertner, D., & Weber, U. (2004). The heidelberg ion therapy center. Radiotherapy and Oncology, 73, S186-S190. doi:10.1016/s0167-8140(04)80046-xHueso-González, F., Rabe, M., Ruggieri, T. A., Bortfeld, T., & Verburg, J. M. (2018). A full-scale clinical prototype for proton range verification using prompt gamma-ray spectroscopy. Physics in Medicine & Biology, 63(18), 185019. doi:10.1088/1361-6560/aad513Kelleter, L., Wrońska, A., Besuglow, J., Konefał, A., Laihem, K., Leidner, J., … Tessonnier, T. (2017). Spectroscopic study of prompt-gamma emission for range verification in proton therapy. Physica Medica, 34, 7-17. doi:10.1016/j.ejmp.2017.01.003Knopf, A.-C., & Lomax, A. (2013). In vivoproton range verification: a review. Physics in Medicine and Biology, 58(15), R131-R160. doi:10.1088/0031-9155/58/15/r131Kozlovsky, B., Murphy, R. J., & Ramaty, R. (2002). Nuclear Deexcitation Gamma‐Ray Lines from Accelerated Particle Interactions. The Astrophysical Journal Supplement Series, 141(2), 523-541. doi:10.1086/340545Krimmer, J., Dauvergne, D., Létang, J. M., & Testa, É. (2018). Prompt-gamma monitoring in hadrontherapy: A review. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 878, 58-73. doi:10.1016/j.nima.2017.07.063Leverington, B. D., Dziewiecki, M., Renner, L., & Runze, R. (2018). A prototype scintillating fibre beam profile monitor for Ion Therapy beams. Journal of Instrumentation, 13(05), P05030-P05030. doi:10.1088/1748-0221/13/05/p05030Mein, S., Choi, K., Kopp, B., Tessonnier, T., Bauer, J., Ferrari, A., … Mairani, A. (2018). Fast robust dose calculation on GPU for high-precision 1H, 4He, 12C and 16O ion therapy: the FRoG platform. Scientific Reports, 8(1). doi:10.1038/s41598-018-33194-4Paganetti, H. (2012). Range uncertainties in proton therapy and the role of Monte Carlo simulations. Physics in Medicine and Biology, 57(11), R99-R117. doi:10.1088/0031-9155/57/11/r99Panaino, C., Taylor, M. J., MacKay, R., Merchant, M. J., Price, T., Pheonix, B., & Green, S. (2018). Abstract ID: 171 A Monte Carlo study to reduce range uncertainty in proton beam therapy via prompt gamma-ray detection. Physica Medica, 45, S2. doi:10.1016/j.ejmp.2017.11.027Pinto, M., Bajard, M., Brons, S., Chevallier, M., Dauvergne, D., Dedes, G., … Testa, M. (2014). Absolute prompt-gamma yield measurements for ion beam therapy monitoring. Physics in Medicine and Biology, 60(2), 565-594. doi:10.1088/0031-9155/60/2/565Quarati, F. G. A., Dorenbos, P., van der Biezen, J., Owens, A., Selle, M., Parthier, L., & Schotanus, P. (2013). Scintillation and detection characteristics of high-sensitivity CeBr3 gamma-ray spectrometers. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 729, 596-604. doi:10.1016/j.nima.2013.08.005Dal Bello, R., Magalhaes Martins, P., & Seco, J. (2018). CeBr3scintillators for4He prompt gamma spectroscopy: Results from a Monte Carlo optimization study. Medical Physics, 45(4), 1622-1630. doi:10.1002/mp.12795Dal Bello, R., Magalhaes Martins, P., Graça, J., Hermann, G., Kihm, T., & Seco, J. (2019). Results from the experimental evaluation of CeBr scintillators for He prompt gamma spectroscopy. Medical Physics, 46(8), 3615-3626. doi:10.1002/mp.13594Roemer, K., Pausch, G., Bemmerer, D., Berthel, M., Dreyer, A., Golnik, C., … Fiedler, F. (2015). Characterization of scintillator crystals for usage as prompt gamma monitors in particle therapy. Journal of Instrumentation, 10(10), P10033-P10033. doi:10.1088/1748-0221/10/10/p10033Testa, M., Bajard, M., Chevallier, M., Dauvergne, D., Freud, N., Henriquet, P., … Testa, E. (2010). Real-time monitoring of the Bragg-peak position in ion therapy by means of single photon detection. Radiation and Environmental Biophysics, 49(3), 337-343. doi:10.1007/s00411-010-0276-2Tommasino, F., Scifoni, E., & Durante, M. (2015). New Ions for Therapy. International Journal of Particle Therapy, 2(3), 428-438. doi:10.14338/ijpt-15-00027.1Vanstalle, M., Mattei, I., Sarti, A., Bellini, F., Bini, F., Collamati, F., … Tessa, C. L. (2017). Benchmarking Geant4 hadronic models for prompt‐ γ monitoring in carbon ion therapy. Medical Physics, 44(8), 4276-4286. doi:10.1002/mp.12348Verburg, J. M., Riley, K., Bortfeld, T., & Seco, J. (2013). Energy- and time-resolved detection of prompt gamma-rays for proton range verification. Physics in Medicine and Biology, 58(20), L37-L49. doi:10.1088/0031-9155/58/20/l37Verburg, J. M., & Seco, J. (2014). Proton range verification through prompt gamma-ray spectroscopy. Physics in Medicine and Biology, 59(23), 7089-7106. doi:10.1088/0031-9155/59/23/7089Werner, F., Bauer, C., Bernhard, S., Capasso, M., Diebold, S., Eisenkolb, F., … Zietara, K. (2017). Performance verification of the FlashCam prototype camera for the Cherenkov Telescope Array. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 876, 31-34. doi:10.1016/j.nima.2016.12.05

Experimental comparison of photon versus particle computed tomography to predict tissue relative stopping powers

Purpose: Measurements comparing relative stopping power (RSP) accuracy of state-of-the-art systems representing single-energy and dual-energy computed tomography (SECT/DECT) with proton CT (pCT) and helium CT (HeCT) in biological tissue samples. Methods: We used 16 porcine and bovine samples of various tissue types and water, covering an RSP range from 0.90urn:x-wiley:00942405:media:mp15283:mp15283-math-00010.06 to 1.78 urn:x-wiley:00942405:media:mp15283:mp15283-math-00020.05. Samples were packed and sealed into 3D-printed cylinders (urn:x-wiley:00942405:media:mp15283:mp15283-math-0003 cm, urn:x-wiley:00942405:media:mp15283:mp15283-math-0004 cm) and inserted into an in-house designed cylindrical polymethyl methacrylate (PMMA) phantom (urn:x-wiley:00942405:media:mp15283:mp15283-math-0005 cm, urn:x-wiley:00942405:media:mp15283:mp15283-math-0006 cm). We scanned the phantom in a commercial SECT and DECT (120 kV; 100 and 140 kV/Sn (tin-filtered)); and acquired pCT and HeCT (urn:x-wiley:00942405:media:mp15283:mp15283-math-0007 MeV/u, 2urn:x-wiley:00942405:media:mp15283:mp15283-math-0008 steps, urn:x-wiley:00942405:media:mp15283:mp15283-math-0009 (p)/urn:x-wiley:00942405:media:mp15283:mp15283-math-0010 (He) particles/projection) with a particle imaging prototype. RSP maps were calculated from SECT/DECT using stoichiometric methods and from pCT/HeCT using the DROP-TVS algorithm. We estimated the average RSP of each tissue per modality in cylindrical volumes of interest and compared it to ground truth RSP taken from peak-detection measurements. Results: Throughout all samples, we observe the following root-mean-squared RSP prediction errors urn:x-wiley:00942405:media:mp15283:mp15283-math-0011 combined uncertainty from reference measurement and imaging: SECT 3.10urn:x-wiley:00942405:media:mp15283:mp15283-math-00122.88%, DECT 0.75urn:x-wiley:00942405:media:mp15283:mp15283-math-00132.80%, pCT 1.19urn:x-wiley:00942405:media:mp15283:mp15283-math-0014 2.81%, and HeCT 0.78urn:x-wiley:00942405:media:mp15283:mp15283-math-00152.81%. The largest mean errors urn:x-wiley:00942405:media:mp15283:mp15283-math-0016 combined uncertainty per modality are SECT 8.22 urn:x-wiley:00942405:media:mp15283:mp15283-math-00172.79% in cortical bone, DECT 1.74urn:x-wiley:00942405:media:mp15283:mp15283-math-00182.00% in back fat, pCT 1.80 urn:x-wiley:00942405:media:mp15283:mp15283-math-00194.27% in bone marrow, and HeCT 1.37urn:x-wiley:00942405:media:mp15283:mp15283-math-00204.25% in bone marrow. Ring artifacts were observed in both pCT and HeCT reconstructions, imposing a systematic shift to predicted RSPs. Conclusion: Comparing state-of-the-art SECT/DECT technology and a pCT/HeCT prototype, DECT provided the most accurate RSP prediction, closely followed by particle imaging. The novel modalities pCT and HeCT have the potential to further improve on RSP accuracies with work focusing on the origin and correction of ring artifacts. Future work will study accuracy of proton treatment plans using RSP maps from investigated imaging modalities

Optimization of carbon ion and proton treatment plans using the raster-scanning technique for patients with unresectable pancreatic cancer

Background: The aim of the thesis is to improve radiation plans of patients with locally advanced, unresectable pancreatic cancer by using carbon ion and proton beams. Patients and methods: Using the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) a total of 50 treatment plans have been created for five patients with the dose schedule 15 × 3 Gy(RBE). With reference to the anatomy, five field configurations were considered to be relevant. The plans were analyzed with respect to dose distribution and individual anatomy, and compared using a customized index. Results: Within the index the three-field configurations yielded the best results, though with a high variety of score points (field setup 5, carbon ion: median 74 (range 48–101)). The maximum dose in the myelon is low (e.g. case 3, carbon ion: 21.5 Gy(RBE)). A single posterior field generally spares the organs at risk, but the maximum dose in the myelon is high (e.g. case 3, carbon ion: 32.9 Gy(RBE)). Two oblique posterior fields resulted in acceptable maximum doses in the myelon (e.g. case 3, carbon ion: 26.9 Gy(RBE)). The single-field configuration and the two oblique posterior fields had a small score dispersion (carbon ion: median 66 and 58 (range 62–72 and 40–69)). In cases with topographic proximity of the organs at risk to the target volume, the single-field configuration scored as well as the three-field configurations. Conclusion: In summary, the three-field configurations showed the best dose distributions. A single posterior field seems to be robust and beneficial in case of difficult topographical conditions and topographical proximity of organs at risk to the target volume. A setup with two oblique posterior fields is a reasonable compromise between three-field and single-field configurations

Phase space generation for Proton and carbon ion Beams for external Users' applications at the heidelberg ion Therapy center

In the field of radiation therapy, accurate and robust dose calculation is required. For this purpose, precise modeling of the irradiation system and reliable computational platforms are needed. At the Heidelberg Ion Therapy Center (HIT), the beamline has been already modeled in the FLUKA Monte Carlo (MC) code. However, this model was kept confidential for disclosure reasons and was not available for any external team. The main goal of this study was to create efficiently phase space (PS) files for proton and carbon ion beams, for all energies and foci available at HIT. PSs are representing the characteristics of each particle recorded (charge, mass, energy, coordinates, direction cosines, generation) at a certain position along the beam path. In order to achieve this goal, keeping a reasonable data size but maintaining the requested accuracy for the calculation, we developed a new approach of beam PS generation with the MC code FLUKA. The generated PSs were obtained using an infinitely narrow beam and recording the desired quantities after the last element of the beamline, with a discrimination of primaries or secondaries. In this way, a unique PS can be used for each energy to accommodate the different foci by combining the narrow-beam scenario with a random sampling of its theoretical Gaussian beam in vacuum. PS can also reproduce the different patterns from the delivery system, when properly combined with the beam scanning information. MC simulations using PS have been compared to simulations, including the full beamline geometry and have been found in very good agreement for several cases (depth dose distributions, lateral dose profiles), with relative dose differences below 0.5%. This approach has also been compared with measured data of ion beams with different energies and foci, resulting in a very satisfactory agreement. Hence, the proposed approach was able to fulfill the different requirements and has demonstrated its capability for application to clinical treatment fields. It also offers a powerful tool to perform investigations on the contribution of primary and secondary particles produced in the beamline. These PSs are already made available to external teams upon request, to support interpretation of their measurements

Late normal tissue response in the rat spinal cord after carbon ion irradiation

Background: The present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the “clinical research group ion beam therapy” funded by the German Research Foundation (DFG, KFO 214). Methods and materials: Dose–response curves for the endpoint radiation-induced myelopathy were determined at 6 different positions (LET 16–99 keV/μm) within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon ions. Based on the tolerance dose TD50 of carbon ions and photons, the relative biological effectiveness (RBE) was determined and compared with predictions of the local effect model (LEM I and IV). Within a longitudinal magnetic resonance imaging (MRI)-based study the temporal development of radiation-induced changes in the spinal cord was characterized. To test the protective potential of the ACE (angiotensin converting enzyme)-inhibitor ramipril™, an additional dose–response experiment was performed. Results: The RBE-values increased with LET and the increase was found to be larger for smaller fractional doses. Benchmarking the RBE-values as predicted by LEM I and LEM IV with the measured data revealed that LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low-LET region. Characterization of the temporal development of radiation-induced changes with MRI demonstrated a shorter latency time for carbon ions, reflected on the histological level by an increased vessel perforation after carbon ion as compared to photon irradiations. For the ACE-inhibitor ramipril™, a mitigative rather than protective effect was found. Conclusions: This comprehensive study established a large and consistent RBE data base for late effects in the rat spinal cord after carbon ion irradiation which will be further extended in ongoing studies. Using MRI, an extensive characterization of the temporal development of radiation-induced alterations was obtained. The reduced latency time for carbon ions is expected to originate from a dynamic interaction of various complex pathological processes. A dominant observation after carbon ion irradiation was an increase in vessel perforation preferentially in the white matter. To enable a targeted pharmacological intervention more details of the molecular pathways, responsible for the development of radiation-induced myelopathy are required

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation

Background: Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions. Methods: Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O2) vs. normoxic conditions (21% O2). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi). Results: The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition. Conclusions: Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy

Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines

<p>Abstract</p> <p>Introduction</p> <p>The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT).</p> <p>Materials and methods</p> <p>Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX.</p> <p>Results</p> <p>Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines - again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA.</p> <p>Conclusion</p> <p>Our <it>in vitro </it>data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines.</p