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.

Effect of Radiation Therapy Techniques on Outcome in N3-positive IIIB Non-small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. MATERIALS AND METHODS: From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) delivered to 48 (62.3%) and 29 (37.7%) patients, respectively. Weekly docetaxel/paclitaxel plus cisplatin (67, 87.0%) was the most common concurrent chemotherapy regimen. RESULTS: The median age and clinical target volume (CTV) were 60 years and 288.0 cm3, respectively. Patients receiving IMRT had greater disease extent in terms of supraclavicular lymph node (SCN) involvement and CTV > or = 300 cm3. The median follow-up time was 21.7 months. Fortyfive patients (58.4%) experienced disease progression, most frequently distant metastasis (39, 50.6%). In-field locoregional control, progression-free survival (PFS), and overall survival (OS) rates at 2 years were 87.9%, 38.7%, and 75.2%, respectively. Although locoregional control was similar between RT techniques, patients receiving IMRT had worse PFS and OS, and SCN metastases from the lower lobe primary tumor and CTV > or = 300 cm3were associated with worse OS. The incidence and severity of toxicities did not differ significantly between RT techniques. CONCLUSION: IMRT could lead to similar locoregional control and toxicity, while encompassing a greater disease extent than 3D-CRT. The decision to apply IMRT should be made carefully after considering oncologic outcomes associated with greater disease extent and cost.

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 an Offline Based Internal Organ Motion Verification System during Treatment Using Sequential Cine EPID Images / 의학물리

Verification of internal organ motion during treatment and its feedback is essential to accurate dose delivery to the moving target. We developed an offline based internal organ motion verification system (IMVS) using cine EPID images and evaluated its accuracy and availability through phantom study. For verification of organ motion using live cine EPID images, a pattern matching algorithm using an internal surrogate, which is very distinguishable and represents organ motion in the treatment field, like diaphragm, was employed in the self-developed analysis software. For the system performance test, we developed a linear motion phantom, which consists of a human body shaped phantom with a fake tumor in the lung, linear motion cart, and control software. The phantom was operated with a motion of 2 cm at 4 sec per cycle and cine EPID images were obtained at a rate of 3.3 and 6.6 frames per sec (2 MU/frame) with 1,024x768 pixel counts in a linear accelerator (10 MVX). Organ motion of the target was tracked using self-developed analysis software. Results were compared with planned data of the motion phantom and data from the video image based tracking system (RPM, Varian, USA) using an external surrogate in order to evaluate its accuracy. For quantitative analysis, we analyzed correlation between two data sets in terms of average cycle (peak to peak), amplitude, and pattern (RMS, root mean square) of motion. Averages for the cycle of motion from IMVS and RPM system were 3.98+/-0.11 (IMVS 3.3 fps), 4.005+/-0.001 (IMVS 6.6 fps), and 3.95+/-0.02 (RPM), respectively, and showed good agreement on real value (4 sec/cycle). Average of the amplitude of motion tracked by our system showed 1.85+/-0.02 cm (3.3 fps) and 1.94+/-0.02 cm (6.6 fps) as showed a slightly different value, 0.15 (7.5% error) and 0.06 (3% error) cm, respectively, compared with the actual value (2 cm), due to time resolution for image acquisition. In analysis of pattern of motion, the value of the RMS from the cine EPID image in 3.3 fps (0.1044) grew slightly compared with data from 6.6 fps (0.0480). The organ motion verification system using sequential cine EPID images with an internal surrogate showed good representation of its motion within 3% error in a preliminary phantom study. The system can be implemented for clinical purposes, which include organ motion verification during treatment, compared with 4D treatment planning data, and its feedback for accurate dose delivery to the moving target.

Development of Movement Analysis Program and Its Feasibility Test in Streotactic Body Radiation Threrapy / 의학물리

Respiratory gated radiation therapy and stereotactic body radiation therapy require identical tumor motions during each treatment with the motion detected in treatment planning CT. Therefore, this study developed a tumor motion monitoring and analysis system during the treatments employing RPM data, gated setup OBI images and a data analysis software. A respiratory training and guiding program which improves the regularity of breathing was used to patients. The breathing signal was obtained by RPM and the recorded data in the 4D console was read after treatment. The setup OBI images obtained gated at 0% and 50% of breathing phases were used to detect the tumor motion range in crenio-caudal direction. By matching the RPM data recorded at the OBI imaging time, a factor which converts the RPM motion to the tumor motion was computed. RPM data was entered to the institute developed data analysis software and the maximum, minimum, average of the breathing motion as well as the standard deviation of motion amplitude and period was computed. The computed result is exported in an excel file. The conversion factor was applied to the analyzed data to estimate the tumor motion. The accuracy of the developed method was tested by using a moving phantom, and the efficacy was evaluated for 10 stereotactic body radiation therapy patients. For the sine wave motion of the phantom with 4 sec of period and 2 cm of peak-to-peak amplitude, the measurement was slightly larger (4.052 sec) and the amplitude was smaller (1.952 cm). For patient treatment, one patient was evaluated not to qualified to SBRT due to the usability of the breathing, and in one patient case, the treatment was changed to respiratory gated treatment due the larger motion range of the tumor than treatment planed motion. The developed method and data analysis program was useful to estimate the tumor motion during treatment.

Analysis of changes in dose distribution due to respiration during IMRT

PURPOSE: Intensity modulated radiation therapy (IMRT) is a high precision therapy technique that can achieve a conformal dose distribution on a given target. However, organ motion induced by respiration can result in significant dosimetric error. Therefore, this study explores the dosimetric error that result from various patterns of respiration. MATERIALS AND METHODS: Experiments were designed to deliver a treatment plan made for a real patient to an in-house developed motion phantom. The motion pattern; the amplitude and period as well as inhale-exhale period, could be controlled by in-house developed software. Dose distribution was measured using EDR2 film and analysis was performed by RIT113 software. Three respiratory patterns were generated for the purpose of this study; first the 'even inhale-exhale pattern', second the slightly long exhale pattern (0.35 seconds longer than inhale period) named 'general signal pattern', and third a 'long exhale pattern' (0.7 seconds longer than inhale period). One dimensional dose profile comparisons and gamma index analysis on 2 dimensions were performed RESULTS: In one-dimensional dose profile comparisons, 5% in the target and 30% dose difference at the boundary were observed in the long exhale pattern. The center of high dose region in the profile was shifted 1 mm to inhale (caudal) direction for the 'even inhale-exhale pattern', 2 mm and 5 mm shifts to exhale (cranial) direction were observed for 'slightly long exhale pattern' and 'long exhale pattern', respectively. The areas of gamma index >1 were 11.88%, 15.11%, and 24.33% for 'even inhale-exhale pattern', 'general pattern', and 'long exhale pattern', respectively. The long exhale pattern showed largest errors. CONCLUSION: To reduce the dosimetric error due to respiratory motions, controlling patient's breathing to be closer to even inhaleexhale period is helpful with minimizing the motion amplitude.

Digital Tomosynthesis for Patient Alignment System Using Half-fan Mode CBCT Projection Images / 의학물리

To generate on-board digital tomosynthesis (DTS) for three-dimensionalimage-guided radiation therapy (IGRT) as an alternative to conventional portal imaging or on-board cone-beam computed tomography (CBCT), two clinical cases (liver and bladder) were selected to illustrate the capabilities of on-board DTS for IGRT. DTS images were generated from subsets of CBCT projection data (45, 162 projections) using half-fan mode scanning with a Feldkamp-type reconstruction algorithm. Digital tomosynthesis slices appeared similar to coincident CBCT planes and yielded substantially more anatomic information. Improved bony and soft-tissue visibility in DTS images is likely to improve target localization compared with radiographic verification techniques and might allow for daily localization of a soft-tissue target. Digital tomosynthesis might allow targeting of the treatment volume on the basis of daily localization.

The Clinical Implementation of 2D Dose Distribution QA System for the Patient Specific Respiratory-gated Radiotherapy / 의학물리

Emerging technologies such as four-dimensional computed tomography (4D CT) is expected to allow clinicians to accurately model interfractional motion and to quantitatively estimate internal target volumes (ITVs) for radiation therapy involving moving targets. A need exists for a 4D radiation therapy quality assurance (QA) device that can incorporate and analyze the patient specific intrafractional motion as it relate to dose delivery and respiratory gating. We built a 4D RT prototype device and analyzed the patient-specific 4D radiation therapy QA for 2D dose distributions successfully. With more improvements, the 4D RT QA prototype device could be an integral part of a 4D RT decision process to confirm the dose delivery.

Evaluation of the Positional Uncertainty of a Liver Tumor using 4-Dimensional Computed Tomography and Gated Orthogonal Kilovolt Setup Images / 대한방사선종양학회지

PURPOSE: In order to evaluate the positional uncertainty of internal organs during radiation therapy for treatment of liver cancer, we measured differences in inter- and intra-fractional variation of the tumor position and tidal amplitude using 4-dimentional computed radiograph (DCT) images and gated orthogonal setup kilovolt (KV) images taken on every treatment using the on board imaging (OBI) and real time position management (RPM) system. MATERIALS AND METHODS: Twenty consecutive patients who underwent 3-dimensional (3D) conformal radiation therapy for treatment of liver cancer participated in this study. All patients received a 4DCT simulation with an RT16 scanner and an RPM system. Lipiodol, which was updated near the target volume after transarterial chemoembolization or diaphragm was chosen as a surrogate for the evaluation of the position difference of internal organs. Two reference orthogonal (anterior and lateral) digital reconstructed radiograph (DRR) images were generated using CT image sets of 0% and 50% into the respiratory phases. The maximum tidal amplitude of the surrogate was measured from 3D conformal treatment planning. After setting the patient up with laser markings on the skin, orthogonal gated setup images at 50% into the respiratory phase were acquired at each treatment session with OBI and registered on reference DRR images by setting each beam center. Online inter-fractional variation was determined with the surrogate. After adjusting the patient setup error, orthogonal setup images at 0% and 50% into the respiratory phases were obtained and tidal amplitude of the surrogate was measured. Measured tidal amplitude was compared with data from 4DCT. For evaluation of intra-fractional variation, an orthogonal gated setup image at 50% into the respiratory phase was promptly acquired after treatment and compared with the same image taken just before treatment. In addition, a statistical analysis for the quantitative evaluation was performed. RESULTS: Medians of inter-fractional variation for twenty patients were 0.00 cm (range, -0.50 to 0.90 cm), 0.00 cm (range, -2.40 to 1.60 cm), and 0.00 cm (range, -1.10 to 0.50 cm) in the X (transaxial), Y (superior-inferior), and Z (anterior-posterior) directions, respectively. Significant inter-fractional variations over 0.5 cm were observed in four patients. Min addition, the median tidal amplitude differences between 4DCTs and the gated orthogonal setup images were -0.05 cm (range, -0.83 to 0.60 cm), -0.15 cm (range, -2.58 to 1.18 cm), and -0.02 cm (range, -1.37 to 0.59 cm) in the X, Y, and Z directions, respectively. Large differences of over 1 cm were detected in 3 patients in the Y direction, while differences of more than 0.5 but less than 1 cm were observed in 5 patients in Y and Z directions. Median intra-fractional variation was 0.00 cm (range, -0.30 to 0.40 cm), -0.03 cm (range, -1.14 to 0.50 cm), 0.05 cm (range, -0.30 to 0.50 cm) in the X, Y, and Z directions, respectively. Significant intra-fractional variation of over 1 cm was observed in 2 patients in Y direction. CONCLUSION: Gated setup images provided a clear image quality for the detection of organ motion without a motion artifact. Significant intra- and inter-fractional variation and tidal amplitude differences between 4DCT and gated setup images were detected in some patients during the radiation treatment period, and therefore, should be considered when setting up the target margin. Monitoring of positional uncertainty and its adaptive feedback system can enhance the accuracy of treatments.

Analysis of the Imaging Dose for IGRT/Gated Treatments / 대한방사선종양학회지

PURPOSE: The introduction of image guided radiation therapy/four-dimensional radiation therapy (IGRT/4DRT) potentially increases the accumulated dose to patients from imaging and verification processes as compared to conventional practice. It is therefore essential to investigate the level of the imaging dose to patients when IGRT/4DRT devices are installed. The imaging dose level was monitored and was compared with the use of pre-IGRT practice. MATERIALS AND METHODS: A four-dimensional CT (4DCT) unit (GE, Ultra Light Speed 16), a simulator (Varian Acuity) and Varian IX unit with an on-board imager (OBI) and cone beam CT (CBCT) were installed. The surface doses to a RANDO phantom (The Phantom Laboratory, Salem, NY USA) were measured with the newly installed devices and with pre-existing devices including a single slice CT scanner (GE, Light Speed), a simulator (Varian Ximatron) and L-gram linear accelerator (Varian, 2100C Linac). The surface doses were measured using thermo luminescent dosimeters (TLDs) at eight sites-the brain, eye, thyroid, chest, abdomen, ovary, prostate and pelvis. RESULTS: Compared to imaging with the use of single slice non-gated CT, the use of 4DCT imaging increased the dose to the chest and abdomen approximately ten-fold (1.74+/-0.34 cGy versus 23.23+/-3.67 cGy ). Imaging doses with the use of the Acuity simulator were smaller than doses with the use of the Ximatron simulator, which were 0.91+/-0.89 cGy versus 6.77+/-3.56 cGy, respectively. The dose with the use of the electronic portal imaging device (EPID; Varian IX unit) was approximately 50% of the dose with the use of the L-gram linear accelerator (1.83+/-0.36 cGy versus 3.80+/-1.67 cGy). The dose from the OBI for fluoroscopy and low-dose mode CBCT were 0.97+/-0.34 cGy and 2.3+/-0.67 cGy, respectively. CONCLUSION: The use of 4DCT is the major source of an increase of the radiation (imaging) dose to patients. OBI and CBCT doses were small, but the accumulated dose associated with everyday verification need to be considered

A Dose Volume Histogram Analyzer Program for External Beam Radiotherapy / 대한방사선종양학회지

PURPOSE: To provide a simple research tool that may be used to analyze a dose volume histogram from different radiation therapy planning systems for NTCP (Normal Tissue Complication Probability), OED (Organ Equivalent Dose) and so on. MATERIALS AND METHODS: A high-level computing language was chosen to implement Niemierko's EUD, Lyman-Kutcher-Burman model's NTCP, and OED. The requirements for treatment planning analysis were defined and the procedure, using a developed GUI based program, was described with figures. The calculated data, including volume at a dose, dose at a volume, EUD, and NTCP were evaluated by a commercial radiation therapy planning system, Pinnacle (Philips, Madison, WI, USA) for comparison. RESULTS: The volume at a special dose and a dose absorbed in a volume on a dose volume histogram were successfully extracted using DVH data of several radiation planning systems. EUD, NTCP and OED were successfully calculated using DVH data and some required parameters in the literature. CONCLUSION: A simple DVH analyzer program was developed and has proven to be a useful research tool for radiation therapy.

Efficacy of a Respiratory Training System on the Regularity of Breathing / 대한방사선종양학회지

PURPOSE: In order to enhance the efficiency of respiratory gated 4-dimensional radiation therapy for more regular and stable respiratory period and amplitude, a respiration training system was designed, and its efficacy was evaluated. MATERIALS AND METHODS: The experiment was designed to measure the difference in respiration regularity following the use of a training system. A total of 11 subjects (9 volunteers and 2 patients) were included in the experiments. Three different breathing signals, including free breathing (free-breathing), guided breathing that followed training software (guided-breathing), and free breathing after the guided-breathing (post guided-breathing), were consecutively recorded in each subject. The peak-to-peak (PTP) period of the breathing signal, standard deviation (SD), peak-amplitude and its SD, area of the one cycle of the breathing wave form, and its root mean square (RMS) were measured and computed. RESULTS: The temporal regularity was significantly improved in guided-breathing since the SD of breathing period reduced (free-breathing 0.568 vs guided-breathing 0.344, p=0.0013). The SD of the breathing period representing the post guided-breathing was also reduced, but the difference was not statistically significant (free-breathing 0.568 vs. guided-breathing 0.512, p=ns). Also the SD of measured amplitude was reduced in guided-breathing (free-breathing 1.317 vs. guided-breathing 1.068, p=0.187), although not significant. This indicated that the tidal volume for each breath was kept more even in guided-breathing compared to free-breathing. There was no change in breathing pattern between free-breathing and guided-breathing. The average area of breathing wave form and its RMS in postguided-breathing, however, was reduced by 7% and 5.9%, respectively. CONCLUSION: The guided-breathing was more stable and regular than the other forms of breathing data. Therefore, the developed respiratory training system was effective in improving the temporal regularity and maintaining a more even tidal volume.