ESF-EMBO symposium "molecular biology and innovative therapies in sarcomas of childhood and adolescence" Sept 29–Oct 4, Polonia Castle Pultusk, Poland

Rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are among the most common pediatric sarcomas (Arndt et al., 2012). Despite sarcomas representing a highly heterogeneous group of tumors, ES and alveolar RMS (ARMS) typically share one common genetic characteristic, namely a specific chromosomal translocation (Helman and Meltzer, 2003; Lessnick and Ladanyi, 2012). These translocations generate fusion proteins, which are composed of two transcription factors (TF). Typically, one TF is a developmentally regulated factor that is essential for proper specification of a given lineage and provides the DNA-binding domain, while the partner TF contributes a transactivation domain that drives aberrant expression of target genes. Based on these common genetic characteristics, the first ESF-EMBO research conference entitled “Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence” with special focus on RMS and ES was held at the Polonia Castle in Pultusk, Poland. The conference gathered 70 participants from more than 15 countries and several continents representing most research groups that are active in this field

New technique for bunch shape flattening

A technique for increasing the bunching factor (Bf) is described. Typically in booster-type synchrotrons, it is important to reduce the transverse space-charge tune shift. One means to achieve this is to increase the ratio of average to peak longitudinal charge density. Essentially, the idea is to create hollow bunches by sweeping high-harmonic empty buckets into the particle beam prior to bunching and acceleration. Successful beam experiments are reported with supporting LONG1D simulation studies performed on the CERN PS Booster for both single and dual rf cases. The longitudinally hollow bunches also benefit the receiving ring during the double batch transfer where half of the PS has to wait 1.2 seconds at low energy for the second injection. A 15th harmonic rf system was used to form the empty buckets. Simulations show that for the single harmonic case, Bf is increased from 0.28 to 0.38, and for the dual harmonic one, Bf is increased from 0.45 to 0.55 (values at 100 MeV). The flattening technique has been tested successfully with the first harmonic to 1 GeV and to 100 MeV for dual harmonic acceleration

Beam Dynamics in High Intensity Cyclotrons Including Neighboring Bunch Effects: Model, Implementation and Application

Space charge effects, being one of the most significant collective effects, play an important role in high intensity cyclotrons. However, for cyclotrons with small turn separation, other existing effects are of equal importance. Interactions of radially neighboring bunches are also present, but their combined effects has not yet been investigated in any great detail. In this paper, a new particle in cell based self-consistent numerical simulation model is presented for the first time. The model covers neighboring bunch effects and is implemented in the three-dimensional object-oriented parallel code OPAL-cycl, a flavor of the OPAL framework. We discuss this model together with its implementation and validation. Simulation results are presented from the PSI 590 MeV Ring Cyclotron in the context of the ongoing high intensity upgrade program, which aims to provide a beam power of 1.8 MW (CW) at the target destination

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR).

BACKGROUND Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. METHODS Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. RESULTS Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively. CONCLUSION Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups

Analytic fluid theory of beam spiraling in high-intensity cyclotrons

Using a two-dimensional fluid description, we investigate the nonlinear radial-longitudinal dynamics of intense beams in isochronous cyclotrons in the nonrelativistic limit. With a multiscale analysis separating the time scale associated with the betatron motion and the slower time scale associated with space-charge effects, we show that the longitudinal-radial vortex motion can be understood in the frame moving with the charged beam as the nonlinear advection of the beam by the E×B velocity field, where E is the electric field due to the space charge and B is the external magnetic field. This interpretation provides simple explanations for the stability of round beams and for the development of spiral halos in elongated beams. By numerically solving the nonlinear advection equation for the beam density, we find that it is also in quantitative agreement with results obtained in particle-in-cell simulations

Intensity Modulated Radiotherapy (IMRT) and Fractionated Stereotactic Radiotherapy (FSRT) for children with head-and-neck-rhabdomyosarcoma

<p>Abstract</p> <p>Background</p> <p>The present study evaluates the outcome of 19 children with rhabdomyosarcoma of the head-and-neck region treated with Intensity Modulated Radiotherapy (IMRT) or Fractionated Stereotactic Radiotherapy (FSRT) between August 1995 and November 2005.</p> <p>Methods</p> <p>We treated 19 children with head-and-neck rhabdomyosarcoma with FSRT (n = 14) or IMRT (n = 5) as a part of multimodal therapy. Median age at the time of radiation therapy was 5 years (range 2–15 years). All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols.</p> <p>Median size of treatment volume for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 Gy – 54 Gy) using a median fractionation of 5 × 1,8 Gy/week (range 1,6 Gy – 1,8 Gy).</p> <p>The median time interval between primary diagnosis and radiation therapy was 5 months (range 3–9 months).</p> <p>Results</p> <p>After RT, the 3- and 5-year survival rate was 94%. The 3- and 5-year actuarial local control rate after RT was 89%.</p> <p>The actuarial freedom of distant metastases rate at 3- and 5-years was 89% for all patients.</p> <p>Radiotherapy was well tolerated in all children and could be completed without interruptions > 4 days. No toxicities >CTC grade 2 were observed. The median follow-up time after RT was 17 months.</p> <p>Conclusion</p> <p>IMRT and FSRT lead to excellent outcome in children with head-and-neck RMS with a low incidence of treatment-related side effects.</p

The PS complex produces the nominal LHC beam

The LHC [1] will be supplied, via the SPS, with protons from the pre-injector chain comprising Linac2, PS Booster (PSB) and PS. These accelerators have under-gone a major upgrading programme [2] during the last five years so as to meet the stringent requirements of the LHC. These imply that many high-intensity bunches of small emittance and tight spacing (25 ns) be available at the PS extraction energy (25 GeV). The upgrading project involved an increase of Linac2 current, new RF systems in the PSB and the PS, raising the PSB energy from 1 to 1.4 GeV, two-batch filling of the PS and the installation of high-resolution beam profile measurement devices. With the project entering its final phase and most of the newly installed hardware now being operational, the emphasis switches to producing the nominal LHC beam and tackling the associated beam physics problems. While a beam with transverse characteristics better than nominal has been obtained, the longitudinal density still needs to be increased. An alternative scheme to produce the 25 ns bunch spacing is outlined, together with other promising developments