RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro study at the Proton Medical Research Center at the University of Tsukuba.

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBE(plateau)) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBE(plateau) was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBE(plateau) was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBE(plateau) or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba.

Lineal energy-based evaluation of oxidative DNA damage induced by proton beams and X-rays.

PURPOSE: To determine the oxidative capabilities of proton beams compared to X-rays based on lineal energy (y). MATERIALS AND METHODS: Microdosimetry was used to determine y-values of 155 MeV protons. Salmon testes deoxyribonucleic acid (ST-DNA) in solution and human tumor cells (MOLT-4) were irradiated with 200 kV X-rays (X) or 155 MeV protons at their plateau (P) and near their Bragg-peak (B). 8-Hydroxydeoxyguanosine (8-OHdG) production was determined by high performance liquid chromatography. Double-strand breaks (DSB) in ST-DNA were evaluated by agarose gel electrophoresis and DSB in cell nuclei were evaluated by immunocytochemical analysis of phosphorylated histone H2AX (γH2AX) foci. Edaravone was used as a radical scavenger. RESULTS: 8-OHdG yields in ST-DNA were significantly higher with X than with P or B, and they were significantly higher with P than with B. DSB yields in ST-DNA were higher with P than with B or X, although not statistically significant, and were nearly equal with B and X. Although γH2AX foci formation in MOLT-4 cells after each irradiation type was nearly identical, the addition of edaravone significantly inhibited foci formation only with X. CONCLUSIONS: Our results indicated that radical-induced indirect DNA damage was significantly lower with proton beams than with X-rays.

Displacement of hepatic tumor at time to exposure in end-expiratory-triggered-pulse proton therapy.

PURPOSE: This study is to evaluate reproducibility of hepatic tumors in end-expiration and end-inspiration on free-breathing, also measure shift of hepatic tumor location in pulsed proton beams exposure in end-expiration in order to estimate feasible planning target volume (PTV) margin. MATERIALS AND METHODS: Pairs (1232) of anterior and lateral radiographs from 30 patients (628 end-expiration and 604 end-inspiration phases) were analyzed using fiducial markers adjacent to the tumors. By using the co-ordinates of the marker centroid of mass related to the isocenter, intrafractional variation was compared in end-expiration and end-inspiration, and a feasible PTV margin was generated using the measured motion. RESULTS: The average internal motion in end-expiration was 1.1mm, which was significantly smaller than that in end-inspiration. The mean deviation from the plan was -0.1, 0.3, and 0.1mm in the left-right (LR), cranio-cepharal (CC), and anterior-posterior (AP) directions, respectively. The estimated PTV margins were 3.2, 3.5, and 4.6mm, in the LR, CC, and AP directions, respectively. CONCLUSIONS: It was indicated that localization of the targets was more reproducibility in end-expiration than that in end-inspiration. Also, feasible and practical margin values were obtained. These should contribute accuracy of respiration synchronized proton radiotherapy for liver tumors.

Feasibility study on using imaging plates to estimate thermal neutron fluence in neutron-gamma mixed fields.

In current radiotherapy, neutrons are produced in a photonuclear reaction when incident photon energy is higher than the threshold. In the present study, a method of discriminating the neutron component was investigated using an imaging plate (IP) in the neutron-gamma-ray mixed field. Two types of IP were used: a conventional IP for beta- and gamma rays, and an IP doped with Gd for detecting neutrons. IPs were irradiated in the mixed field, and the photo-stimulated luminescence (PSL) intensity of the thermal neutron component was discriminated using an expression proposed herein. The PSL intensity of the thermal neutron component was proportional to thermal neutron fluence. When additional irradiation of photons was added to constant neutron irradiation, the PSL intensity of the thermal neutron component was not affected. The uncertainty of PSL intensities was approximately 11.4 %. This method provides a simple and effective means of discriminating the neutron component in a mixed field.

Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines.

PURPOSE: To clarify the properties of clinical high-energy protons by comparing with clinical high-energy X-rays. MATERIALS AND METHODS: Human tumor cell lines, ONS76 and MOLT4, were irradiated with 200 MeV protons or 10 MV X-rays. In situ DNA double-strand breaks (DDSB) induction was evaluated by immunocytochemical staining of phosphorylated histone H2AX (γ-H2AX). Apoptosis was measured by flow-cytometry after staining with Annexin V. The relative biological effectiveness (RBE) was obtained by clonogenic survival assay. RESULTS: DDSB induction was significantly higher for protons than X-rays with average ratios of 1.28 (ONS76) and 1.59 (MOLT4) at 30 min after irradiation. However the differences became insignificant at 6 h. Also, apoptosis induction in MOLT4 cells was significantly higher for protons than X-rays with an average ratio of 2.13 at 12 h. However, the difference became insignificant at 20 h. RBE values of protons to X-rays at 10% survival were 1.06 ±â€Š0.04 and 1.02 ±â€Š0.15 for ONS76 and MOLT4, respectively. CONCLUSIONS: Cell inactivation may differ according to different timings and/or endpoints. Proton beams demonstrated higher cell inactivation than X-rays in the early phases. These data may facilitate the understanding of the biological properties of clinical proton beams.

Waveform simulation based on 3D dose distribution for acoustic wave generated by proton beam irradiation.

A pulsed proton beam is capable of generating an acoustic wave when it is absorbed by a medium. This phenomenon suggests that the acoustic waveform produced may well include information on the three-dimensional (3D) dose distribution of the proton beam. We simulated acoustic waveforms by using a transmission model based on the Green function and the 3D dose distribution. There was reasonable agreement between the calculated and measured results. The results obtained confirm that the acoustic waveform includes information on the dose distribution.