Jiwon Sung

Estimation of the risk of secondary malignancy arising from whole-breast irradiation: comparison of five radiotherapy modalities, including TomoHDA

The risk of secondary cancer from radiation treatment remains a concern for long-term breast cancer survivors, especially those treated with radiation at the age younger than 45 years. Treatment modalities optimally maximize the dose delivery to the tumor while minimizing radiation doses to neighboring organs, which can lead to secondary cancers. A new TomoTherapy treatment machine, TomoHDATM, can treat an entire breast with two static but intensity-modulated beams in a slice-by-slice fashion. This feature could reduce scattered and leakage radiation doses. We compared the plan quality and lifetime attributable risk (LAR) of a second malignancy among five treatment modalities: three-dimensional conformal radiation therapy, field-in-field forward-planned intensity-modulated radiation therapy, inverse-planned intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, and TomoDirect mode on the TomoHDA system. Ten breast cancer patients were selected for retrospective analysis. Organ equivalent doses, plan characteristics, and LARs were compared. Out-of-field organ doses were measured with radio-photoluminescence glass dosimeters. Although the IMRT plan provided overall better plan quality, including the lowest probability of pneumonitis, it caused the second highest LAR. The TomoTherapy plan provided plan quality comparable to the IMRT plan and posed the lowest total LAR to neighboring organs. Therefore, it can be a better treatment modality for younger patients who have a longer life expectancy.

Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation

Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.

Secondary cancer-incidence risk estimates for external radiotherapy and high-dose-rate brachytherapy in cervical cancer: phantom study

This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various locations inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence during cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary malignancies. PACS number(s): 87.52.-g, 87.52.Px, 87.53.Dq, 87.53.Jw.This study was designed to estimate radiation‐induced secondary cancer risks from high‐dose‐rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out‐of‐field organs were measured at various locations inside an anthropomorphic phantom. Brachytherapy‐associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out‐of‐field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy‐induced secondary cancer incidence during cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy‐associated secondary malignancies. PACS number(s): 87.52.‐g, 87.52.Px, 87.53.Dq, 87.53.Jw

Inhibition of brain tumor cell proliferation by alternating electric fields

This study was designed to investigate the mechanism by which electric fields affect cell function, and to determine the optimal conditions for electric field inhibition of cancer cell proliferation. Low-intensity (<2 V/cm) and intermediate-frequency (100–300 kHz) alternating electric fields were applied to glioblastoma cell lines. These electric fields inhibited cell proliferation by inducing cell cycle arrest and abnormal mitosis due to the malformation of microtubules. These effects were significantly dependent on the intensity and frequency of applied electric fields.

Generation of high-contrast, 30 fs, 1.5 PW laser pulses

A high-contrast, 30 fs, 1.5 PW Ti:sapphire laser has been developed for research on high field physics. The maximum output energy of 60.2 J was obtained from a booster amplifier pumped by four frenquency-doubled Nd:glass laser systems. Parasitic lasing was suppressed by index matching fluid with absorption dye and the careful manipulation of the time delay between the seed and pump pulses. After compression, the measured pulse duration was 30.2 ± 1.8 fs, and the output energy was 44.5 J, yielding a peak power of about 1.5 PW. A saturable absorber and two ultrafast Pockels cells were installed in the front-end system for the minimization of the amplified spontaneous emission (ASE) and pre-pulse intensity. An adaptive optics system was implemented for obtaining the near diffraction-limited focal spot.

Selective toxicity of tumor treating fields to melanoma: an in vitro and in vivo study

Tumor treating fields (TTFs) are a newly developed cancer therapy technology using an alternating electric field that may be a possible candidate for overcoming the limitations of conventional treatment methods currently used in cancer treatment. Although clinical results using TTFs appear promising, concerns regarding side effects must be clarified to demonstrate the effectiveness of this treatment method. To investigate the side effects of TTF treatment, the damage to normal cell lines and normal tissue of a mouse model was compared with the damage to tumor cells and tumors in a mouse model after TTF treatment. No serious damage was found in the normal cells and normal tissues of the mouse model, suggesting that the side effects of TTF treatment may not be serious. Our evidence based on in vitro and in vivo experiments suggests that TTF may cause selective damage to cancer cells, further demonstrating the potential of TTF as an attractive alternative to conventional cancer treatment modalities.

Gold nanoparticles as a potent radiosensitizer in neutron therapy

The purpose of this study was to investigate the potential of gold nanoparticles as radiosensitizer for use in neutron therapy against hepatocellular carcinoma. The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with γ and neutron radiation in the presence or absence of gold nanoparticles. Effects were evaluated by transmission electron microscopy, cell survival, cell cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly enhanced the radiosensitivity of Huh7 and HepG2 cells to γ-rays by 1.41- and 1.16-fold, respectively, and by 1.80- and 1.35-fold to neutron radiation, which has high linear energy transfer. Accordingly, exposure to neutron radiation in the presence of gold nanoparticles induced cell cycle arrest, DNA damage, and cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of gold nanoparticles to amplify the effective dose from neutron radiation more efficiently. The data suggest that gold nanoparticles may be clinically useful in combination therapy against hepatocellular carcinoma by enhancing the toxicity of radiation with high linear energy transfer.

Evaluation of performance of portable respiratory monitoring system based on micro-electro-mechanical-system for respiratory gated radiotherapy

In respiratory-gated radiotherapy of patients with lung or liver cancer, the patient’s respiratory pattern and repeatability are important factors affecting therapy accuracy; it has been reported that these factors can be controlled if patients undergo respiration training. As such, this study evaluates the feasibility of micro-electro-mechanical-system (MEMS) in radiotherapy by investigating the effect of radiation on a miniature portable respiratory monitoring system based on the MEMS system, which is currently under development. Using a patient respiration simulation phantom, the time-acceleration graph measured by a normal sensor according to the phantom’s respiratory movement before irradiation and the change in this graph with accumulated dose were compared using the baseline slope and the change in amplitude and period of the sine wave. The results showed that with a 400Gy accumulated dose in the sensor, a baseline shift occurred and both the amplitude and period changed. As a result, if the MEMS is applied in respiratory-gated radiotherapy, the sensor should be replaced after use with roughly 6-10 patients so as to ensure continued therapy accuracy, based on the characteristics of the sensor itself. In the future, a more diverse range of sensors should be similarly evaluated.

SU-E-T-322: The Evaluation of the Gafchromic EBT3 Film in Low Dose 6 MV X-Ray Beams with Different Scanning Modes.

PURPOSE We have evaluated the response of the Gafchromic EBT3 film in low dose for 6 MV x-ray beams with two scanning modes, the reflection scanning mode and the transmission scanning mode. METHODS We irradiated the Gafcromic EBT3 film using a 60 degree enhanced dynamic wedge (EDW) with 6 MV x-ray beams from Clinac iX Linear accelerator (Varian Medical Systems, Palo Alto, CA). The irradiated Gafchromic EBT3 film was scanned with different scanning modes, the reflection scanning mode and the transmission scanning mode. The scanned Gafchromic EBT3 film was analyzed with MATLAB. RESULTS When 7.2 cGy was irradiated to the Gafchromic EBT3 film, the uncertainty was 0.54 cGy with reflection scanning mode and was 0.88 cGy with transmission scanning mode. When 24 cGy was irradiated to the Gafchromic EBT3 film, the uncertainty was similar to the case of 7.2 cGy irradiation showing 0.51 cGy of uncertainty with reflection scanning mode and 0.87 cGy of uncertainty with transmission scanning mode. The result suggests that the reflection mode should be used in Gafchromic EBT3 film for low irradiation. CONCLUSION The result suggests that the reflection mode should be used in Gafchromic EBT3 film for low irradiation.

SU-E-T-306: Study of the Reduction Technique for the Secondary Cancer Risk Due to Cone Beam CT in Image Guided Radiotherapy

PURPOSE This study evaluated the effectiveness of a thin lead sheet based simple shielding method for imaging doses from cone beam computed tomography (CBCT) in image-guided radiotherapy (IGRT). METHODS The entire body, except for the region scanned by CBCT, was shielded by wrapping in a 2 mm lead sheet. Reduction of secondary doses from CBCT was measured using a radio-photoluminescence glass dosimeter (RPLGD) placed inside an anthropomorphic phantom and changes in secondary cancer risk due to the shielding effect were estimated using BEIR VII model. RESULTS Doses to out-of-field organs for head-and-neck, chest, and pelvis scans were decreased 15∼100 %, 23∼90 %, and 23∼98 %, respectively, and the average reductions in lifetime secondary cancer risk due to the 2 mm lead shielding were 1.61, 10.4, and 12.8 persons per 100,000, respectively. CONCLUSION This study suggests that a simple thin lead sheet based shielding method results in a non-negligible reduction of secondary doses to out-of-field regions for CBCT.