Recent developments in radiotherapy for hepatocellular carcinoma

The role of radiotherapy in practice is mainly palliative. According to the Practice Guidelines for Management of Hepatocellular Carcinoma (2009) developed by the Korean Liver Cancer Study Group and the National Cancer Center, Korea, radiotherapy can be applied for 1) refractoriness to trans-catheter hepatic arterial chemo-embolization, 2) portal vein tumor thrombosis, and 3) palliative therapy to reduce the symptoms caused by hepatocellular carcinoma. Radiotherapy is one of the most rapidly developing fields of medical research. Recent advances in intensity-modulated radiotherapy, image-guided radiotherapy, and respiratory-gated radiotherapy technologies have enabled more accurate and precise radiation delivery for the treatment of hepatocellular carcinoma. Proton therapy is also emerging as a candidate therapy for ablative measures for patients ineligible for other curative local therapies. Due to recent advances in radiotherapy technologies, radiotherapy for hepatocellular carcinoma has been evolving into stereotactic ablative radiotherapy, which delivers an ablative dose of radiation in 1 to 4 sessions. Clinical series have confirmed that it is safe in Child-Pugh A patients and local control is sustained. The possibility for performing phase 3 randomized clinical trials involving the radiotherapy modality has increased with those advances. Not merely palliative, the role of radiotherapy in the treatment of hepatocellular carcinoma will be expanded to potentially curative therapy in patients who are ineligible for other curative local therapies.

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.

The Analysis of Predictive Factors for the Identification of Patients Who Could Benefit from Respiratory-Gated Radiotherapy in Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: 4DCT scans performed for radiotherapy were retrospectively analyzed to assess the possible benefits of respiratory gating in non-small cell lung cancer (NSCLC) and established the predictive factors for identifying patients who could benefit from this approach. MATERIALS AND METHODS: Three treatment planning was performed for 15 patients with stage I~III NSCLC using different planning target volumes (PTVs) as follows: 1) PTVroutine, derived from the addition of conventional uniform margins to gross tumor volume (GTV) of a single bin, 2) PTVall phases (patient-specific PTV), derived from the composite GTV of all 6 bins of the 4DCT, and 3) PTVgating, derived from the composite GTV of 3 consecutive bins at end-exhalation. RESULTS: The reductions in PTV were 43.2% and 9.5%, respectively, for the PTVall phases vs. PTVroutine and PTVgating vs. PTVall phases. Compared to PTVroutine, the use of PTVall phases and PTVgating reduced the mean lung dose (MLD) by 18.1% and 21.6%, and V20 by 18.2% and 22.0%, respectively. Significant correlations were seen between certain predictive factors selected from the tumor mobility and volume analysis, such as the 3D mobility vector, the reduction in 3D mobility and PTV with gating, and the ratio of GTV overlap between 2 extreme bins and additional reductions in both MLD and V20 with gating. CONCLUSION: The additional benefits with gating compared to the use of patient-specific PTV were modest; however, there were distinct correlations and differences according to the predictive factors. Therefore, these predictive factors might be useful for identifying patients who could benefit from respiratory-gated radiotherapy.

Development of Respiratory Signal Analysis Program for Accurate Phase Reassignment in 4D CT Reconstruction / 의학물리

Patient's respiration can have an effect on movement of tumor range and peripheral organs. Therefore, the respiratory signal was acquired by relation between external markers and movement of patient's abdomen during radiational therapy in order to minimize the effect of respiration. Based on this technique, many studies of rational therapy to irradiate at particular part of stable respiratory signals have executed and they have been clinically applied. Nevertheless, the phase-based method is preferred to the amplitude-based method for the rational therapy related to respiration. Because stabilization of the respiratory signal are limited. In this study, a in-house respiratory signal analysis program was developed for the phase reassignment and the analysis of the irregular respiratory signals. Various irregular respiratory patterns was obtained from clinical experimental volunteers. After then, the in-house program analyzed the factors affecting to phase assignment which is directly related to irradiated sector. Subsequently, accuracy of phase assignment was improved with removement of irregular signals by self-developed algorithm. This study is considered to be useful for not only image reconstruction and elevation of irradiating accuracy through phase assignment of RPM system but also analysis of respiratory signals. Moreover, development of 4D CT image is planed with phantom researches or clinical experiments based on this program.

Analysis on the Decrease of Planning Target Volume in the Case of Lung Radiation Surgery with the Application of Respiratory Gated Radiotherpy Method / 의학물리

The application of a respiratory gated radiotherpy method to the lung radiation surgery was evaluated compared with the conventional method in which the whole tumor motion range is considered in the delineation of PTV (Planning target volume). The four dimensional CT simulation images were acquired for the five NSCLC (Non-small cell lung cancer) patients for radiation surgery. The respiratory gated plan was prepared with the 50% phase CT images and the conventional method was planned based on the ITV (Internal target volume) which include all the target volumes created in each phase CT images within a whole respiratory period. The DVH (Dose volume histogram) of OAR (Organ at risk) which calculated in each method was compared for the evaluation of the plan properness. The relative decrease of OARs' DVH were verified in the application of respiratory gated method. The average decrease rate were 16.88+/-9.97% in the bronchus, 34.13+/-19.15% in the spinal cord, 28.42+/-18.49% in the chest wall and 32.48+/-16.66% in the lung. Based on these results, we can verified the applicability and the effectiveness of the respiratory gated method in the lung radiation surgery.

Evaluation of Difference between Skin Motion and Tumor Motion for Respiration Gated Radiotherapy / 의학물리

Accounting for tumor motion in treatment planning and delivery is one of the most recent and significant challenges facing radiotherapy. The purpose of this study was to investigate the correlation and clarified the relationship between the motion of an external marker using the Real?Time Position Management (RPM) System and an internal organ motion signal obtained fluoroscope. We enrolled 10 patients with locally advanced lung cancer and liver cancer, retrospectively. The external marker was a plastic box, which is part of the RPM used to track the patient's respiration. We investigated the quantitatively correlation between the motions of an external marker with RPM and internal motion with fluoroscope. The internal fiducial motion is predominant in the caraniocaudal direction, with a range of 1.3~3.5 cm with fluoroscopic unit. The external fiducial motion is predominant in the caraniocaudal direction, with a range of 0.43~2.19 cm with RPM gating. The two measurements ratio is from 1.31 to 5.56. When the regularization guided standard deviation is from 0.08 to 0.87, mean 0.204 cm, except only for patients #3 separated by a mean 0.13 cm, maximum of 0.23 cm. This result is a good correlation between internal tumor motion imaged by fluoroscopic unit and external marker motion with RPM during expiration within 0.23 cm. We have demonstrated that gating may be best performed but special attention should be paid to gating for patients whose fiducials do not move in synchrony, because targeting on the correct phase difference alone would not guarantee that the entire tumor volume is within the treatment field.

Application of Real-Time Tumor-Tracking and Gated Radiotherapy System for Unresectable Pancreatic Cancer

Herein is reported our experience of radiation therapy using a real-time tumor-tracking and gated radiotherapy (RTRT) system for inoperable pancreatic cancer. Three unresectable pancreatic cancer patients were treated with intraoperative electron beam radiation therapy, at the time of open biopsy, and postoperative external beam radiation therapy using an RTRT system with a 2.0 mm diameter gold ball implanted into the pancreas. The total BED's (alpha/beta=10) was intended to be equivalent to that of delivering 60 Gy by 2.0 Gy/fraction, while the actual dose schedules were individualized. The movement of the pancreas was analyzed based on the 3-dimensional marker positions during the RTRT. The side effects and tumor responses were evaluated. During the RTRT course, the average movement of markers in the x (left to right), y (cranial to caudal) and z (dorsal to ventral) directions were 3.0 mm (1.7- 5.2 mm), 5.2 mm (3.5 - 6.8 mm) and 3.5 mm (2.7 - 5.1 mm), respectively. During and after the course of postoperative radiation therapy, no acute side effects of RTOG grade II or higher were detected. The objective tumor responses, as evaluated by CT scans 3 months after the treatment, were 2 partial responses and no response in one patient. Using the RTRT technique the margin of treatment planning and the possible errors in target localization were reduced, and the 3-dimensional movement of the internal marker implanted in the pancreas was able to be analyzed.