Is higher dose always the right answer in stereotactic body radiation therapy for small hepatocellular carcinoma?

PURPOSE: This study was conducted to compare clinical outcomes and treatment-related toxicities after stereotactic body radiation therapy (SBRT) with two different dose regimens for small hepatocellular carcinomas (HCC) ≤3 cm in size. Materials and. METHODS: We retrospectively reviewed 44 patients with liver-confined HCC treated between 2009 and 2014 with SBRT. Total doses of 45 Gy (n = 10) or 60 Gy (n = 34) in 3 fractions were prescribed to the 95% isodose line covering 95% of the planning target volume. Rates of local control (LC), intrahepatic failure-free survival (IHFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Median follow-up was 29 months (range, 8 to 64 months). Rates at 1 and 3 years were 97.7% and 95.0% for LC, 97.7% and 80.7% for OS, 76% and 40.5% for IHFFS, and 87.3% and 79.5% for DMFS. Five patients (11.4%) experienced degradation of albumin-bilirubin grade, 2 (4.5%) degradation of Child-Pugh score, and 4 (9.1%) grade 3 or greater laboratory abnormalities within 3 months after SBRT. No significant difference was seen in any oncological outcomes or treatment-related toxicities between the two dose regimens. Conclusions: SBRT was highly effective for local control without severe toxicities in patients with HCC smaller than 3 cm. The regimen of a total dose of 45 Gy in 3 fractions was comparable to 60 Gy in efficacy and safety of SBRT for small HCC.

MEASUREMENT OF NEUTRON AMBIENT DOSE EQUIVALENT IN PROTON RADIOTHERAPY WITH LINE-SCANNING AND WOBBLING MODE TREATMENT SYSTEM.

The primary objective of this study was to measure secondary neutron dose during proton therapy using a detector that covers the entire neutron energy range produced in proton therapy. We analyzed and compared the neutron dose during proton treatment with passive scattering and line scanning. The neutron ambient dose equivalents were measured with a 190 MeV wobbling and line-scanning proton beam. The center of a plastic water phantom (30 × 30 × 60 cm3) was placed at the isocenter. A Wide-Energy Neutron Detection Instrument (WENDI-2) was located 1m from the isocenter at four different angles (0°, 45°, 90° and 135°). Both wobbling and line-scanning modes of a multipurpose and pencil beam scanning dedicated nozzles were used to obtain a spread-out Bragg peak with 10-cm-width for the measurements. The ambient dose equivalent H*(10) value was normalized by the proton therapeutic dose at the isocenter. For wobbling mode and line-scanning mode, the highest H*(10) values were 1.972 and 0.099 mSv/Gy, respectively. We successfully measured the neutron ambient dose equivalents at six positions generated by a 190 MeV proton beam using wobbling and line-scanning mode with the WENDI-2. These reference data could be used for neutron dose reduction methods and other analysis for advanced proton treatment in the near future.

Preclinical investigation for developing injectable fiducial markers using a mixture of BaSO4 and biodegradable polymer for proton therapy.

PURPOSE: The aim of this study is to investigate the use of mixture of BaSO4 and biodegradable polymer as an injectable nonmetallic fiducial marker to reduce artifacts in x-ray images, decrease the absorbed dose distortion in proton therapy, and replace permanent metal markers. METHODS: Two samples were made with 90 wt. % polymer phosphate buffer saline (PBS) and 10 wt. % BaSO4 (B1) or 20 wt. % BaSO4 (B2). Two animal models (mice and rats) were used. To test the injectability and in vivo gelation, a volume of 200 µl at a pH 5.8 were injected into the Sprague-Dawley rats. After sacrificing the rats over time, the authors checked the gel morphology. Detectability of the markers in the x-ray images was tested for two sizes (diameters of 1 and 2 mm) for B1 and B2. Four samples were injected into BALB/C mice. The polymer mixed with BaSO4 transform from SOL at 20 °C with a pH of 6.0 to GEL in the living body at 37 °C with a pH of 7.4, so the size of the fiducial marker could be controlled by adjusting the injected volume. The detectability of the BaSO4 marker was measured in x-ray images of cone beam CT (CBCT), on-board imager [anterior-posterior (AP), lateral], and fluoroscopy (AP, lateral) using a Novalis-TX (Varian Medical Systems, Palo Alto, CA) repeatedly over 4 months. The volume, HU, and artifacts for the markers were measured in the CBCT images. Artifacts were compared to those of gold marker by analyzing the HU distribution. The dose distortion in proton therapy was computed by using a Monte Carlo (MC) code. A cylindrical shaped marker (diameter: 1 or 2 mm, length: 3 mm) made of gold, stainless-steel [304], titanium, and 20 wt. % BaSO4 was positioned at the center of the spread-out Bragg peak (SOBP) in parallel or perpendicular to the beam entrance. The dose distortion was measured on the depth dose profile across the markers. RESULTS: Transformation to GEL and the biodegradation were verified. All BaSO4 markers could be detected in the CBCT. In the OBI and fluoroscopy images, all markers visible in the AP, but only B2(2 mm) could be identified in the lateral images. Changes of BaSO4 position were not detected in vivo (mice). The volume of the markers decreased by up to 65% and the HU increased by 22%, on average. The mean HU values around the B1, B2, and gold markers were 121.30 [standard deviation (SD): 54.86], 126.31 (SD: 62.13), and 1070.7 (SD: 235.16), respectively. The MC-simulated dose distortion for the BaSO4 markers was less than that of the commercially used markers. The dose reduction due to the gold marker was largest (15.05%) followed by stainless steel (7.92%) and titanium (6.92%). Dose reduction by B2 (2 mm) was 4.75% and 0.53% in parallel and perpendicular orientations, respectively. CONCLUSIONS: BaSO4 mixed with PBS is a good contrast agent in biodegradable polymer marker because of minimal artifacts in x-ray images and minimal dose reduction in proton therapy. The flexibility of the size is considered to be an advantage of this material over solid type fiducials.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

PURPOSE: The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. MATERIALS AND METHODS: The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. RESULTS: The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. CONCLUSION: The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Development of the DVH management software for the biologically-guided evaluation of radiotherapy plan.

PURPOSE: To develop the dose volume histogram (DVH) management software which guides the evaluation of radiotherapy (RT) plan of a new case according to the biological consequences of the DVHs from the previously treated patients. MATERIALS AND METHODS: We determined the radiation pneumonitis (RP) as an biological response parameter in order to develop DVH management software. We retrospectively reviewed the medical records of lung cancer patients treated with curative 3-dimensional conformal radiation therapy (3D-CRT). The biological event was defined as RP of the Radiation Therapy Oncology Group (RTOG) grade III or more. RESULTS: The DVH management software consisted of three parts (pre-existing DVH database, graphical tool, and Pinnacle(3) script). The pre-existing DVH data were retrieved from 128 patients. RP events were tagged to the specific DVH data through retrospective review of patients' medical records. The graphical tool was developed to present the complication histogram derived from the pre-existing database (DVH and RP) and was implemented into the radiation treatment planning (RTP) system, Pinnacle(3) v8.0 (Phillips Healthcare). The software was designed for the pre-existing database to be updated easily by tagging the specific DVH data with the new incidence of RP events at the time of patients' follow-up. CONCLUSION: We developed the DVH management software as an effective tool to incorporate the phenomenological consequences derived from the pre-existing database in the evaluation of a new RT plan. It can be used not only for lung cancer patients but also for the other disease site with different toxicity parameters.

Potentially curative stereotactic body radiation therapy (SBRT) for single or oligometastasis to the lung.

BACKGROUND: To analyze the treatment outcomes of a potentially curative therapy, stereotactic body radiation therapy (SBRT), for patients with single or oligometastasis to the lungs. MATERIAL AND METHODS: Sixty-seven metastatic lung lesions in 57 patients were treated with SBRT between September 2001 and November 2010. All patients had single or oligo-metastasis to the lungs following a meticulous clinical work-up, including PET-CT scans. The lungs were the most common primary organ (33 lesions, 49.3%), followed by the head and neck (11 lesions, 16.4%), the liver (nine lesions, 13.5%), the colorectum (seven lesions, 10.4%), and other organs (seven lesions, 10.4%). Three different fractionation schedules were used: 50 Gy/5 fractions to four lesions (6.0%); 60 Gy/5 fractions to 44 lesions (65.7%); and 60 Gy/4 fractions to 19 lesions (28.3%). RESULTS: Local tumor progression occurred in three lesions (4.5%). The three-year actuarial local control rate was 94.5%. Tumors larger than or equal to 2.5 cm showed poorer local control (98.3% vs. 77.8%, p <0.01). Metastatic tumors from the liver and colorectum showed lower local control rates than those from other organs (77.8%, 85.7%, and 100%, p =0.04). The two-year overall survival rate was 57.2%. Patients with tumors smaller than 2.5 cm had more favorable survival rates (64.0% vs. 38.9% at two-year, p =0.032). Patients with extrathoracic disease had poorer survival rates (66.1% vs. 0% at two-year, p =0.003). Patients with disease-free intervals longer than two years showed a trend toward good prognosis (71.1% vs. 51.1% at two-year, p =0.106). Grade 2 lung toxicity occurred in four patients (6.0%). One patient experienced Grade 5 lung toxicity following SBRT. CONCLUSION: SBRT for single or oligo-metastasis to the lung seems quite effective and safe. Tumor size, disease-free interval, and presence of extrathoracic disease are prognosticators for survival.

Comparison of film dosimetry techniques used for quality assurance of intensity modulated radiation therapy.

PURPOSE: Accurate dosimetry is essential to ensure the quality of advanced radiation treatments, such as intensity modulated radiation therapy (IMRT). Therefore, a comparison study was conducted to assess the accuracy of various film dosimetry techniques that are widely used in clinics. METHODS: A simulated IMRT plan that produced an inverse pyramid dose distribution in a perpendicular plane of the beam axis was designed with 6 MV x rays to characterize the large contribution of scattered photons to low dose regions. Three film dosimetry techniques, EDR2, EDR2 with low-energy photon absorption lead filters (EDR2 WF), and GafChromic EBT, were compared to ionization chamber measurements as well as Monte Carlo (MC) simulations. The accuracy of these techniques was evaluated against the ionization chamber data. Two-dimensional comparisons with MC simulation results were made by computing the gamma index (gamma) with criteria ranging from 2% of dose difference or 2 mm of distance to agreement (2%/2 mm) to 4%/4 mm on the central vertical plane (20 x 20 cm2) of a square solid water phantom. Depth doses and lateral profiles at depths of 5, 10, and 15 cm were examined to characterize the deviation of film measurements and MC predictions from ionization chamber measurements. RESULTS: In depth dose comparisons, the deviation between the EDR2 films was 9% in the low dose region and 5% in high dose region, on average. With lead filters, the average deviation was reduced to -1.3% and -0.3% in the low dose and high dose regions, respectively. EBT film results agreed within 1.5% difference on average with ionization chamber measurements in low and high dose regions. In two-dimensional comparisons with MC simulation, EDR2 films passed gamma tests with a 2%/2 mm criterion only in the high dose region (gamma < or = 1, total of 63.06% of the tested region). In the low dose region, EDR2 films passed gamma tests with 3%/3 mm criterion (gamma < or = 1, total of 98.4% of the tested region). For EDR2 WF and GafChromic EBT films, gamma tests with a 2% /2 mm criterion (gamma < or = 1) in the tested area was 97.3% and 96.8% of the tested region, respectively. CONCLUSIONS: The EDR2 film WF and GafChromic EBT film achieved an average accuracy level of 1.5% against an ionization chamber. These two techniques agreed with the MC prediction in 2%/2mm criteria evaluated by the gamma index, whereas EDR2 without filters achieved an accuracy level of 3%/3 mm with the decision criteria of agreement greater than 95% of the tested region. The overall results will provide a useful quantitative reference for IMRT verifications.

Dosimetry in an IMRT phantom designed for a remote monitoring program.

An accurate delivery of prescribed dose is essential to ensure the most successful outcome from advanced radiation treatments such as intensity modulated radiation therapy (IMRT). An anthropomorphic phantom was designed and constructed to conduct a remote-audit program for IMRT treatments. The accuracy of the dosimetry in the phantom was assessed by comparing the results obtained from different detectors with those from Monte Carlo calculations. The developed phantom has a shape of a cylinder with one target and three organs at risk (OARs) inside the unit. The target and OARs were shaped similar to those of nasopharyngeal cancer patients, and manufactured for their identification during computed tomography imaging. The phantom was designed with thermoluminescent dosimeter (TLD) holders that were inserted inside the target and the OARs for the measurements of absolute dose. In addition, the phantom allowed measurements with ionization chambers placed at the TLD locations. As a result, an inter-comparison between the two types of dosimeters was possible. For the measurement of the relative dose distribution across the target and OARs, two film slots were orthogonally placed near the center of the phantom, which also enabled the insertion of inhomogeneities near the target. Measurements with TLDs, provided by Korea Food and Drug Administration and Radiological Physics Center, and measurements with an ionization chamber (IC) were performed in four cases. The first case was one anterior field of 6 MV x rays delivered to the phantom; the second case used the same anterior field, but with inhomogeneities inserted into the phantom. The third case was three fields of 6 MV beams at an equi-gantry angle for the homogeneous phantom, and the fourth case was IMRT delivery to the phantom without inhomogeneities. For each case, measurements with both TLDs and IC were performed. For cases 1-3, theoretical predictions were obtained by using the Monte Carlo (MC) codes (BEAMnrc and DOSXYZnrc6.0). The TLD measurements were larger than the IC readings by 2.2% (1.3-2.5%), 2.2% (1.2-2.9%), and 2.1% (0-3.3%) on average for case 1, case 2 and case 3, respectively. The average deviation between TLDs and MC results was 0.97% (-0.13-2.07%) for the first case, 1.27% (0.34-2.18%) for the second case, and 1.13% (0.31-1.94%) for the third case. The IC reading was less than the MC results; the average deviations were -1.2% (-2.44--0.43%), -0.96% (-1.74 - -0.54%) and -0.94% (-1.53-0.27%) for the first, second, and third cases, respectively. For the IMRT case, the average deviation between IC readings and TLD measurements was 0.5% (-7.0-3.9%). In conclusion, the TLD measurements in the developed phantom agreed with IC and MC results with less than 3% of an average difference. The developed phantom with TLD dosimeters should be useful for remote monitoring of IMRT.

Interfractional dose variation during intensity-modulated radiation therapy for cervical cancer assessed by weekly CT evaluation.

PURPOSE: To investigate the interfractional dose variation of a small-bowel displacement system (SBDS)-assisted intensity-modulated radiation therapy (IMRT) for the treatment of cervical cancer. METHODS: Four computed tomography (CT) scans were carried out in 10 patients who received radiotherapy for uterine cervical cancer. The initial CT was taken by use of the SBDS, before the beginning of radiotherapy, and 3 additional CT scans with the SBDS were done in subsequent weeks. IMRT was planned by use of the initial CT, and the subsequent images were fused with the initial CT set. Dose-volume histogram (DVH) changes of the targets (planning target volume [PTV] = clinical target volume [CTV] + 1.5 cm) and of the critical organs were evaluated after obtaining the volumes of each organ on 4 CT sets. RESULTS: No significant differences were found in PTV volumes. Changes on the DVH of the CTVs were not significant, whereas DVH changes of the PTVs at 40% to 100% of the prescription dose level were significant (V(90%); 2nd week: p = 0.0091, 3rd week: p = 0.0029, 4th week: p = 0.0050). The changes in the small-bowel volume included in the treatment field were significant. These were 119.5 cm3 (range, 26.9-251.0 cm3), 126 cm3 (range, 38.3-336 cm3), 161.9 cm3 (range, 37.7-294.6 cm3), and 149.1 cm3 (range, 38.6-277.8 cm3) at the 1st, 2nd, 3rd, and 4th weeks, respectively, and were significantly correlated with the DVH change in the small bowel, which were significant at the 3rd (V80%; p = 0.0230) and 4th (V80%; p = 0.0263) weeks. The bladder-volume change correlated to the large volume change (>20%) of the small-bowel volume. CONCLUSIONS: Significant DVH differences for the small bowel can result because of interfractional position variations, whereas the DVH differences of the CTV were not significant. Strict bladder-filling control and an accurate margin for the PTV, as well as image-guided position verification, are important to achieve the goal of IMRT.