Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma

Purpose@#This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). @*Materials and Methods@#Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. @*Results@#The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. @*Conclusion@#rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution

PURPOSE: We aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes. MATERIALS AND METHODS: Total 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. RESULTS: Eleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT. CONCLUSION: Both IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Erratum: Acknowledgments correction

The funding acknowledgment in this article was omitted as published.

The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans for prostate cancer

PURPOSE: To evaluate the effect of common three photon energies (6-MV, 10-MV, and 15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate cancer patients. MATERIALS AND METHODS: Twenty patients with prostate cancer treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV IMRT plans for each patient were generated using suitable planning objectives, dose constraints, and 8-field setting. The plans were analyzed in terms of dose-volume histogram for the target coverage, dose conformity, organs at risk (OAR) sparing, and normal tissue integral dose. RESULTS: Regardless of the energies chosen at the plans, the target coverage, conformity, and homogeneity of the plans were similar. However, there was a significant dose increase in rectal wall and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V20 Gy of rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans were increased by up to 13%. CONCLUSION: In this study, 10-MV prostate IMRT plans showed better OAR sparing and less integral doses than the 6-MV. The biological and clinical significance of this finding remains to be determined afterward, considering neutron dose contribution.

PTV Margins for Prostate Treatments with an Endorectal Balloon / 대한방사선종양학회지

PURPOSE: To determine the appropriate prostate planning target volume (PTV) margins for 3-dimensitional (3D) conformal radiotherapy (CRT) and intensity-modulated radiation therapy (IMRT) patients treated with an endorectal balloon (ERB) under our institutional treatment condition. MATERIALS AND METHODS: Patients were treated in the supine position. An ERB was inserted into the rectum with 70 cc air prior to planning a CT scan and then each treatment fraction. Electronic portal images (EPIs) and digital reconstructed radiographs (DRR) of planning CT images were used to evaluate inter-fractional patient's setup and ERB errors. To register both image sets, we developed an in-house program written in visual C++. A new method to determine prostate PTV margins with an ERB was developed by using the common method. RESULTS: The mean value of patient setup errors was within 1 mm in all directions. The ERB inter-fractional errors in the superior-inferior (SI) and anterior-posterior (AP) directions were larger than in the left-right (LR) direction. The calculated 1D symmetric PTV margins were 3.0 mm, 8.2 mm, and 8.5 mm for 3D CRT and 4.1 mm, 7.9 mm, and 10.3 mm for IMRT in LR, SI, and AP, respectively according to the new method including ERB random errors. CONCLUSION: The ERB random error contributes to the deformation of the prostate, which affects the original treatment planning. Thus, a new PTV margin method includes dose blurring effects of ERB. The correction of ERB systematic error is a prerequisite since the new method only accounts for ERB random error.

External Auditing on Absorbed Dose Using a Solid Water Phantom for Domestic Radiotherapy Facilities / 대한방사선종양학회지

PURPOSE: We report the results of an external audit on the absorbed dose of radiotherapy beams independently performed by third parties. For this effort, we developed a method to measure the absorbed dose to water in an easy and convenient setup of solid water phantom. MATERIALS AND METHODS: In 2008, 12 radiotherapy centers voluntarily participated in the external auditing program and 47 beams of X-ray and electron were independently calibrated by the third party's American Association of Physicists in Medicine (AAPM) task group (TG)-51 protocol. Even though the AAPM TG-51 protocol recommended the use of water, water as a phantom has a few disadvantages, especially in a busy clinic. Instead, we used solid water phantom due to its reproducibility and convenience in terms of setup and transport. Dose conversion factors between solid water and water were determined for photon and electron beams of various energies by using a scaling method and experimental measurements. RESULTS: Most of the beams (74%) were within +/-2% of the deviation from the third party's protocol. However, two of 20 X-ray beams and three of 27 electron beams were out of the tolerance (+/-3%), including two beams with a >10% deviation. X-ray beams of higher than 6 MV had no conversion factors, while a 6 MV absorbed dose to a solid water phantom was 0.4% less than the dose to water. The electron dose conversion factors between the solid water phantom and water were determined: The higher the electron energy, the less is the conversion factor. The total uncertainty of the TG-51 protocol measurement using a solid water phantom was determined to be +/-1.5%. CONCLUSION: The developed method was successfully applied for the external auditing program, which could be evolved into a credential program of multi-institutional clinical trials. This dosimetry saved time for measuring doses as well as decreased the uncertainty of measurement possibly resulting from the reference setup in water.

A Comprehensive Computer Program for Monitor Unit Calculation and Beam Data Management: Independent Verification of Radiation Treatment Planning Systems / 의학물리

We developed a user-friendly program to independently verify monitor units (MUs) calculated by radiation treatment planning systems (RTPS), as well as to manage beam database in clinic. The off-axis factor, beam hardening effect, inhomogeneity correction, and the different depth correction were incorporated into the program algorithm to improve the accuracy in calculated MUs. A beam database in the program was supposed to use measured data from routine quality assurance (QA) processes for timely update. To enhance user's convenience, a graphic user interface (GUI) was developed by using Visual Basic for Application. In order to evaluate the accuracy of the program for various treatment conditions, the MU comparisons were made for 213 cases of phantom and for 108 cases of 17 patients treated by 3D conformal radiation therapy. The MUs calculated by the program and calculated by the RTPS showed a fair agreement within +/-3% for the phantom and +/-5% for the patient, except for the cases of extreme inhomogeneity. By using Visual Basic for Application and Microsoft Excel worksheet interface, the program can automatically generate beam data book for clinical reference and the comparison template for the beam data management. The program developed in this study can be used to verify the accuracy of RTPS for various treatment conditions and thus can be used as a tool of routine RTPS QA, as well as independent MU checks. In addition, its beam database management interface can update beam data periodically and thus can be used to monitor multiple beam databases efficiently.

A Comparison of Peripheral Doses Scattered from a Physical Wedge and an Enhanced Dynamic Wedge / 의학물리

In order to evaluate the radio-protective advantage of an enhanced dynamic wedge (EDW) over a physical wedge (PW), we measured peripheral doses scattered from both types of wedges using a 2D array of ion-chambers. A 2D array of ion-chambers was used for this purpose. In order to confirm the accuracy of the device, we first compared measured profiles of open fields with the profiles calculated by our commissioned treatment planning system. Then, we measured peripheral doses for the wedge angles of 15 degrees, 30 degrees, 45 degrees, and 60 degrees at source to surface distances (SSD) of 80 cm and 90 cm. The measured points were located at 0.5 cm depth from 1 cm to 5 cm outside of the field edge. In addition, the measurements were repeated by using thermoluminescence dosimeters (TLD). The peripheral doses of EDW were (1.4% to 11.9%) lower than those of PW (2.5% to 12.4%). At 15 MV energy, the average peripheral doses of both wedges were 2.9% higher than those at 6MV energy. At a small SSD (80 cm vs. 90 cm), peripheral dose differences were more recognizable. The average peripheral doses to the heel direction were 0.9% lower than those to the toe direction. The results from the TLD measurements confirmed these findings with similar tendency. Dynamic wedges can reduce unnecessary scattered doses to normal tissues outside of the field edge in many clinical situations. Such an advantage is more profound in the treatment of steeper wedge angles, and shorter SSD.

Evaluation of Biological Characteristics of Neutron Beam Generated from MC50 Cyclotron / 대한방사선종양학회지

PURPOSE: To evaluate biological characteristics of neutron beam generated by MC50 cyclotron located in the Korea Institute of Radiological and Medical Sciences (KIRAMS). MATERIALS AND METHODS: The neutron beams generated with 15 mm Beryllium target hit by 35 MeV proton beam was used and dosimetry data was measured before in-vitro study. We irradiated 0, 1, 2, 3, 4 and 5 Gy of neutron beam to EMT-6 cell line and surviving fraction (SF) was measured. The SF curve was also examined at the same dose when applying lead shielding to avoid gamma ray component. In the X-ray experiment, SF curve was obtained after irradiation of 0, 2, 5, 10, and 15 Gy. RESULTS: The neutron beams have 84% of neutron and 16% of gamma component at the depth of 2 cm with the field size of 26 x 26 cm2, beam current 20 micro A, and dose rate of 9.25 cGy/min. The SF curve from X-ray, when fitted to linear-quadratic (LQ) model, had 0.611 as alpha/beta ratio (alpha=0.0204, beta=0.0334, R2=0.999, respectively). The SF curve from neutron beam had shoulders at low dose area and fitted well to LQ model with the value of R2 exceeding 0.99 in all experiments. The mean value of alpha and beta were -0.315 (range, -0.254 ~ -0.360) and 0.247 (0.220~0.262), respectively. The addition of lead shielding resulted in no straightening of SF curve and shoulders in low dose area still existed. The RBE of neutron beam was in range of 2.07~2.19 with SF=0.1 and 2.21~2.35 with SF=0.01, respectively. CONCLUSION: The neutron beam from MC50 cyclotron has significant amount of gamma component and this may have contributed to form the shoulder of survival curve. The RBE of neutron beam generated by MC50 was about 2.2.

Patient Setup Aid with Wireless CCTV System in Radiation Therapy / 대한방사선종양학회지

PURPOSE: To develop a wireless CCTV system in semi-beam's eye view (BEV) to monitor daily patient setup in radiation therapy. MATERIALS AND METHODS: In order to get patient images in semi-BEV, CCTV cameras are installed in a custom-made acrylic applicator below the treatment head of a linear accelerator. The images from the cameras are transmitted via radio frequency signal (~2.4 GHz and 10 mW RF output). An expected problem with this system is radio frequency interference, which is solved utilizing RF shielding with Cu foils and median filtering software. The images are analyzed by our custom-made software. In the software, three anatomical landmarks in the patient surface are indicated by a user, then automatically the 3 dimensional structures are obtained and registered by utilizing a localization procedure consisting mainly of stereo matching algorithm and Gauss-Newton optimization. This algorithm is applied to phantom images to investigate the setup accuracy. Respiratory gating system is also researched with real-time image processing. A line-laser marker projected on a patient's surface is extracted by binary image processing and the breath pattern is calculated and displayed in real-time. RESULTS: More than 80% of the camera noises from the linear accelerator are eliminated by wrapping the camera with copper foils. The accuracy of the localization procedure is found to be on the order of 1.5+/-0.7 mm with a point phantom and sub-millimeters and degrees with a custom-made head/neck phantom. With line-laser marker, real-time respiratory monitoring is possible in the delay time of ~0.17 sec. CONCLUSION: The wireless CCTV camera system is the novel tool which can monitor daily patient setups. The feasibility of respiratory gating system with the wireless CCTV is hopeful.