Challenge for Diagnostic Assessment of Deep Learning Algorithm for Metastases Classification in Sentinel Lymph Nodes on Frozen Tissue Section Digital Slides in Women with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients. @*Materials and Methods@#A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve). @*Results@#The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy. @*Conclusion@#In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting

Development of a Multiparametric Magnetic Resonance Imaging-Based Nomogram for Clinically Insignificant Prostate Cancer

Purpose@#Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. @*Materials and Methods@#We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. @*Results@#Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. @*Conclusions@#We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Development of a Multiparametric Magnetic Resonance Imaging-Based Nomogram for Clinically Insignificant Prostate Cancer

Purpose@#Various predictive tools have been developed to predict insignificant prostate cancer (PCa) for active surveillance, however, these models cannot reflect all the refinements of current medicine. Thus, we aimed to develop a novel model to predict clinically insignificant PCa incorporating these factors. @*Materials and Methods@#We developed a novel nomogram to predict the probability of insignificant PCa (total tumor volume less than 2.5 cm3, index tumor volume less than 1.3 cm3, organ confined disease and no Gleason pattern 4 or 5) using preoperative data of 790 Korean patients who underwent radical prostatectomy. To evaluate the predictive accuracy, the area under the receiver operating characteristic curve (AUC) was calculated. Next, the predicted probability versus the actual probability was compared. This examination was performed by calibration plotting using 1,000 bootstrap resamples. @*Results@#Of the 790 patients, 668 (84.6%) had clinically significant PCa, and 122 (15.4%) had insignificant PCa. We developed a novel predictive model for clinically insignificant PCa using clinical stage less than T2a, biopsy Gleason sum less than 7, ratio of positive biopsy cores less than 10%, neutrophil-to-lymphocyte ratio, and multiparametric magnetic resonance imaging (mpMRI) visibility, which discriminated patients with clinically insignificant PCa from those with significant PCa with an AUC of 0.9135 (95% confidence interval, 0.9127–0.9143). The calibration plot showed a well-calibrated prediction that had little over- or underestimation. @*Conclusions@#We proposed a novel predictive model for insignificant PCa to more accurately select patients for active surveillance using the results from mpMRI and prebiopsy laboratory marker.

Liver Laceration with Hemoperitoneum after Cardiopulmonary Resuscitation / 대한구급학회지

It is well known that external chest compression during cardiopulmonary resuscitation is frequently associated with various complications. These complications predominantly involve trauma to the heart, lungs, and chest wall, whereas cases involving intra-abdominal injury are much less frequent. The present report describes a rare case of a female patient with severe hemoperitoneum associated with liver injury after cardiopulmonary resuscitation. Although emergent angiography and embolization of the hepatic artery were performed and transfusion of various kinds of blood products was done continuously, the patient expired the next day.

Fabrication and Optimization of a Fiber-optic Dosimeter for Proton Beam Therapy Dosimetry / 의학물리

In this study, we have fabricated a fiber-optic dosimeter for a proton beam therapy dosimetry. We have measured scintillating lights with the various kinds of organic scintillators and selected the BCF-12 as a sensor-tip material due to its highest light output and peak/plateau ratio. To determine the optimum diameter of BCF-12, we have measured scintillating lights according to the energy losses of proton beams in a water phantom. Also, we determined the adequate length of organic scintillator by measuring scintillating lights according to the incident angles of proton beam. Using an optimized fiber-optic dosimeter, we have measured scintillating lights according to the dose rates and monitor units of proton accelerator.

Dosimetric Influence of Implanted Gold Markers in Proton Therapy for Prostate Cancer / 의학물리

This study examined the dosimetric influence of implanted gold markers in proton therapy and the effects of their positions in the spread-out Bragg peak (SOBP) proton beam. The implanted cylindrical gold markers were 3 mm long and 1.2 mm in diameter. The dosimetric influence of the gold markers was determined with markers at various locations in a proton-beam field. Spatial dose distributions were measured using a three-dimensional moving water phantom and a stereotactic diode detector with an effective diameter of 0.5 mm. Also, a film dosimetry was performed using Gafchromic External Beam Treatment (EBT) film. The GEANT4 simulation toolkit was used for Monte-Carlo simulations to confirm the measurements and to construct the dose-volume histogram with implanting markers. Motion data were obtained from the portal images of 10 patients to investigate the effect of organ motions on the dosimetric influence of markers in the presence of a rectal balloon. The underdosed volume due to a single gold marker, in which the dose was less than 95% of a prescribed amount, was 0.15 cc. The underdosed volume due to the presence of a gold marker is much smaller than the target volume. However, the underdosed volume is inside the gross tumor volume and is not smeared out due to translational prostate motions. The positions of gold markers and the conditions of the proton-beam field give different impacts on the dose distribution of a target with implanted gold markers, and should be considered in all clinical proton-based therapies.

A Study of Radiation Exposure in Proton Therapy Facility / 의학물리

Proton therapy facility, which is recently installed at National Cancer Center in Korea, generally produces a large amount of radiation near cyclotron due to the secondary particles and radioisotopes caused by collision between proton and nearby materials during the acceleration. Although the level of radiation by radioisotope decreases in length of time, radiation exposure problem still exists since workers are easily exposed by a low level of radiation for a long time due to their job assignment for maintenance or repair of the proton facility. In this paper, the working environment near cyclotron, where the highest radiation exposure is expected, was studied by measuring the degree of radiation and its duration for an appropriate level of protective action guide. To do this, we measured the radiation change in the graphite based energy degrader, the efficiency of transmitted beam and relative activation degree of the transmission beam line. The results showed that while the level of radiation exposure around cyclotron and beam line during the operation is much higher than the other radiation therapy facilities, the radiation exposure rate per year is under the limit recommended by the law showing 1~3 mSv/year.

Geometric Calibration of Cone-beam CT System for Image Guided Proton Therapy / 의학물리

According to improved radiation therapy technology such as IMRT and proton therapy, the accuracy of patient alignment system is more emphasized and IGRT is dominated research field in radiation oncology. We proposed to study the feasibility of cone-beam CT system using simple x-ray imaging systems for image guided proton therapy at National Cancer Center. 180 projection views (2,304x3,200, 14 bit with 127 micrometer pixel pitch) for the geometrical calibration phantom and humanoid phantoms (skull, abdomen) were acquired with 2degrees step angle using x-ray imaging system of proton therapy gantry room (360degrees for 1 rotation). The geometrical calibration was performed for misalignments between the x-ray source and the flat-panel detector, such as distances and slanted angle using available algorithm. With the geometrically calibrated projection view, Feldkamp cone-beam algorithm using Ram-Lak filter was implemented for CBCT reconstruction images for skull and abdomen phantom. The distance from x-ray source to the gantry isocenter, the distance from the flat panel to the isocenter were calculated as 1,517.5 mm, 591.12 mm and the rotated angle of flat panel detector around x-ray beam axis was considered as 0.25degrees. It was observed that the blurring artifacts, originated from the rotation of the detector, in the reconstructed toomographs were significantly reduced after the geometrical calibration. The demonstrated CBCT images for the skull and abdomen phantoms are very promising. We performed the geometrical calibration of the large gantry rotation system with simple x-ray imaging devices for CBCT reconstruction. The CBCT system for proton therapy will be used as a main patient alignment system for image guided proton therapy.

Real-time Body Surface Motion Tracking using the Couch Based Computer-controlled Motion Phantom (CBMP) and Ultrasonic Sensor: A Feasibility Study / 의학물리

Respiration gating radiotherapy technique developed in consideration of the movement of body surface and internal organs during respiration, is categorized into the method of analyzing the respiratory volume for data processing and that of keeping track of fiducial landmark or dermatologic markers based on radiography. However, since these methods require high-priced equipments for treatment and are used for the specific radiotherapy. Therefore, we should develop new essential method whilst ruling out the possible problems. This study aims to obtain body surface motion by using the couch based computer-controlled motion phantom (CBMP) and US sensor, and to develop respiration gating techniques that can adjust patients' beds by using opposite values of the data obtained. The CBMP made to measure body surface motion is composed of a BS II microprocessor, sensor, host computer and stepping motor etc. And the program to control and operate it was developed. After the CBMP was adjusted by entering random movement data, and the phantom movements were acquired using the sensors, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using a rabbit, the real-time respiration gating techniques were drawn by operating the phantom with the opposite values of the data. The result of analyzing the acquisition-correction delay time for the data value shows that the data value coincided within 1% and that the acquisition-correction delay time was obtained real-time (2.34 x 10(-4) sec). And the movement was the maximum movement was 6 mm in Z direction, in which the respiratory cycle was 2.9 seconds. This study successfully confirms the clinical application possibility of respiration gating techniques by using a CBMP and sensor.

The Study on the Head and Neck Phantom for Quality Assurance of Intensity Modulated Radiotherapy / 의학물리

For the QA of IMRT treatment of head and neck cancer by using M3 (BrainLAB Inc. Germany), it is not easy to measure delivery dose exactly because the dose attenuation appears by the couch according to the position of table and gantry. In order to solve this problem, we fabricated head and neck phantom which would be implemented on the couch mount of Brain Lab Inc. We investigated dose attenuation by the couch and found the difference of dose distribution by the couch, in the applying this phantom to the clinic. After measurement, we found that point dose attenuation was 35% at maximum and dose difference was 5.4% for a point dose measurement of actual patient quality assurance plan.

Development of Web-based Dosimetry Calibration Program for High Energy Radiation / 의학물리

Absorbed dose dosimetry protocols of high energy photon and electron beams, which are widely used and based on an air kerma calibration factors, have somewhat complex formalism and limitations for improving dosimetric accuracy due to uncertainty of the physical parameters used. Recently the IAEA and the AAPM published the absorbed dose to water-based dosimetry protocol. In this work web-based dose calibration program for IAEA TRS-398 and AAPM TG-51 protocols were developed. This program developed using the Visual C# language can be used in the internet. User selectable dosimetry protocol on the web allows the absorbed dose to water data of the two protocols at a reference point to be easily compared, and enables to conveniently manage and understand the current status of the dosimetry calibration performed at participating institutions in korea. This program and the resultant database from the web-based calibration can be useful in developing new dosimetry protocols in Korea.

Patient Specific Quality Assurance of IMRT: Quantitative Approach Using Film Dosimetry and Optimization / 대한방사선종양학회지

PURPOSE: Film dosimetry as a part of patient specific intensity modulated radiation therapy quality assurance (IMRT QA) was performed to develop a new optimization method of film isocenter offset and to then suggest new quantitative criteria for film dosimetry. MATERIALS AND METHODS: Film dosimetry was performed on 14 IMRT patients with head and neck cancers. An optimization method for obtaining the local minimum was developed to adjust for the error in the film isocenter offset, which is the largest part of the systemic errors. RESULTS: The adjust value of the film isocenter offset under optimization was 1 mm in 12 patients, while only two patients showed 2 mm translation. The means of absolute average dose difference before and after optimization were 2.36 and 1.56%, respectively, and the mean ratios over a 5% tolerance were 9.67 and 2.88%. After optimization, the differences in the dose decreased dramatically. A low dose range cutoff (L-Cutoff) has been suggested for clinical application. New quantitative criteria of a ratio of over a 5%, but less than 10% tolerance, and for an absolute average dose difference less than 3% have been suggested for the verification of film dosimetry. CONCLUSION: The new optimization method was effective in adjusting for the film dosimetry error, and the newly quantitative criteria suggested in this research are believed to be sufficiently accurate and clinically useful.

Patient Specific Quality Assurance of IMRT: Quantitative Approach Using Film Dosimetry and Optimization / 대한방사선종양학회지

PURPOSE: Film dosimetry as a part of patient specific intensity modulated radiation therapy quality assurance (IMRT QA) was performed to develop a new optimization method of film isocenter offset and to then suggest new quantitative criteria for film dosimetry. MATERIALS AND METHODS: Film dosimetry was performed on 14 IMRT patients with head and neck cancers. An optimization method for obtaining the local minimum was developed to adjust for the error in the film isocenter offset, which is the largest part of the systemic errors. RESULTS: The adjust value of the film isocenter offset under optimization was 1 mm in 12 patients, while only two patients showed 2 mm translation. The means of absolute average dose difference before and after optimization were 2.36 and 1.56%, respectively, and the mean ratios over a 5% tolerance were 9.67 and 2.88%. After optimization, the differences in the dose decreased dramatically. A low dose range cutoff (L-Cutoff) has been suggested for clinical application. New quantitative criteria of a ratio of over a 5%, but less than 10% tolerance, and for an absolute average dose difference less than 3% have been suggested for the verification of film dosimetry. CONCLUSION: The new optimization method was effective in adjusting for the film dosimetry error, and the newly quantitative criteria suggested in this research are believed to be sufficiently accurate and clinically useful.

Development of Respiration Gating RT Technique using Moving Phantom and Ultrasound Sensor: a feasibility study / 대한방사선종양학회지

PURPOSE: In radiotherapy of tumors in liver, enough planning target volume (PTV) margins are necessary to compensate breathing-related movement of tumor volumes. To overcome the problems, this study aims to obtain patients' body movements by using a moving phantom and an ultrasonic sensor, and to develop respiration gating techniques that can adjust patients' beds by using reversed values of the data obtained. MATERIALS AND METHODS: The phantom made to measure patients' body movements is composed of a microprocessor (BS II, 20 MHz, 8K Byte), a sensor (Ultra-Sonic, range 3~3 m), host computer (RS232C) and stepping motor (torque 2.3 Kg) etc., and the program to control and operate it was developed. The program allows the phantom to move within the maximum range of 2 cm, its movements and corrections to take place in order, and x, y and z to move successively. After the moving phantom was adjusted by entering random movement data (three dimensional data form with distance of 2 cm), and the phantom movements were acquired using the ultra sonic sensor, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using guinea pigs, the real-time respiration gating techniques were drawn by operating the phantom with the reversed values of the data. RESULTS: The result of analyzing the acquisition-correction delay time for the three types of data values and about each value separately shows that the data values coincided with one another within 1% and that the acquisition-correction delay time was obtained real-time (2.34x10-4 sec). CONCLUSION: This study successfully confirms the clinic application possibility of respiration gating techniques by using a moving phantom and an ultrasonic sensor. With ongoing development of additional analysis system, which can be used in real-time set-up reproducibility analysis, it may be beneficially used in radiotherapy of moving tumors.