Treatment Outcomes after Postoperative Radiotherapy in Triple-Negative Breast Cancer: Multi-Institutional Retrospective Study (KROG 17-05).

BACKGROUND: We designed a multi-institutional retrospective study to investigate the previously unreported failure pattern, survivals, and prognostic factors after postoperative radiotherapy (PORT) in triple negative breast cancer (TNBC) patients in South Korea. MATERIALS AND METHODS: We retrospectively reviewed 699 patients with TNBC who underwent PORT at six institutions between 2008 and 2010. The median follow-up period was 94 months (range: 7-192 months). There were 216, 380, and 100 patients in stages I, II, and III, respectively. RESULTS: After 94 months post-treatment, all patients with pathologic complete remission after neoadjuvant chemotherapy were alive without any failure. Distant metastasis was the main cause of failure. The 5-year overall survival rate was 91.4%, 5-year loco-regional relapse-free survival rate (LRRFS) was 92.3%, 5-year distant metastasis-free survival rate (DMFS) was 89.4%, and 5-year disease-free survival rate (DFS) was 85.2%. On multivariate (Cox) analysis, T and N stages were significant prognostic factors for survival, and lympho-vascular invasion (LVI) was a significant factor for LRRFS and DMFS. Ki-67 expression was significantly associated with LRRFS and DFS. CONCLUSION: We verified that T and N stages, LVI, and Ki-67 expression were significantly associated with survival outcomes after PORT in TNBC.

Regulating interparticle proximity in plasmonic nanosphere aggregates to enhance photoacoustic response and photothermal stability.

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near-infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agent for PA imaging. Silver (Ag), among plasmonic metals, is particularly attractive due to its strongest optical response and highest heat conductivity. Our results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody-like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, our AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high-contrast PA imaging over multiple imaging sessions. Furthermore, we demonstrate the capability of the AgNAs for molecular PA cancer imaging in vivo by incorporating a tumor-targeting peptide moiety.

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

A Technique to Deliver Conformal External Beam Radiation for Squamous Carcinoma of the Penile Glans and Urethra.

This study presents an approach to external beam radiation therapy for treating penile cancer using a small water bath. This modified technique involves the use of an acrylic, cuboid-shaped water bath with dimensions 6 × 6 × 8 cm3. The water bath is filled with readily available saline solution maintained at room temperature. The patient is positioned in the prone position, and the penis is placed within the water bath. The isocenter is set at the center of the water bath, and bilateral beams are positioned at 89.1° and 270.9°. The proposed technique was evaluated based on dose calculations, demonstrating a clinical target volume dose with a Dmax of 103.5% and a Dmin of 100.0% of the prescribed dose. Additionally, the method showed a low organs-at-risk dose, with a Dmean of only 1% for the testicles. The treatment zone inside the water bath also showed a uniform dose distribution. This technique not only offers high treatment efficiency and more accurate dose distribution to the targeted area but also provides additional benefits, including reduced toxicity to organs at risk and increased device utilization efficiency. In conclusion, the proposed modified external beam radiation therapy method presents a promising alternative for patients with penile cancer, enhancing treatment precision and safety.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

Tunable Interparticle Connectivity in Gold Nanosphere Assemblies for Efficient Photoacoustic Conversion.

Manipulating matter at the nanometer scale to create desired plasmonic nanostructures holds great promise in the field of biomedical photoacoustic (PA) imaging. We demonstrate a strategy for regulating PA signal generation from anisotropic nano-sized assemblies of gold nanospheres (Au NSs) by adjusting the inter-particle connectivity between neighboring Au NSs. The inter-particle connectivity is controlled by modulating the diameter and inter-particle spacing of Au NSs in the nanoassemblies. The results indicate that nanoassemblies with semi-connectivity, i.e., assemblies with a finite inter-particle spacing shorter than the theoretical limit of repulsion between nearby Au NSs, exhibit 3.4-fold and 2.4-fold higher PA signals compared to nanoassemblies with no connectivity and full connectivity, respectively. Furthermore, due to the reduced diffusion of Au atoms, the semi-connectivity Au nanoassemblies demonstrate high photodamage threshold and, therefore, excellent photostability at fluences above the current American National Standards Institute limits. The exceptional photostability of the semi-connectivity nanoassemblies highlights their potential to surpass conventional plasmonic contrast agents for continuing PA imaging. Collectively, our findings indicate that semi-connected nanostructures are a promising option for reliable, high-contrast PA imaging applications over multiple imaging sessions due to their strong PA signals and enhanced photostability.

Dummy run quality assurance study in the Korean Radiation Oncology Group 19 - 09 multi-institutional prospective cohort study of breast cancer.

BACKGROUND: The Korean Radiation Oncology Group (KROG) 19 - 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. METHODS: Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. RESULTS: We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss's kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. CONCLUSION: We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 - 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 - 09 study results.

Dose Profile Modulation of Proton Minibeam for Clinical Application.

The feasibility of proton minibeam radiation therapy (pMBRT) using a multislit collimator (MSC) and a scattering device was evaluated for clinical use at a clinical proton therapy facility. We fabricated, through Monte Carlo (MC) simulations, not only an MSC with a high peak-to-valley dose ratio (PVDR) at the entrance of the proton beam, to prevent radiation toxicity, but also a scattering device to modulate the PVDR in depth. The slit width and center-to-center distance of the diverging MSC were 2.5 mm and 5.0 mm at the large end, respectively, and its thickness and available field size were 100 mm and 76 × 77.5 mm2, respectively. Spatially fractionated dose distributions were measured at various depths using radiochromic EBT3 films and also tested on bacterial cells. MC simulation showed that the thicker the MSC, the higher the PVDR at the phantom surface. Dosimetric evaluations showed that lateral dose profiles varied according to the scatterer's thickness, and the depths satisfying PVDR = 1.1 moved toward the surface as their thickness increased. The response of the bacterial cells to the proton minibeams' depth was also established, in a manner similar to the dosimetric pattern. Conclusively, these results strongly suggest that pMBRT can be implemented in clinical centers by using MSC and scatterers.

Active small bowel sparing in intracavitary brachytherapy for cervical cancer.

OBJECTIVE: To propose and evaluate an active method for sparing the small bowel in the treatment field of cervical cancer brachytherapy by prone position procedure. METHODS: The prone position procedure consists of five steps: making bladder empty, prone-positioning a patient on belly board, making the small bowel move to abdomen, filling the bladder with Foley catheter and finally turning the patient into the supine position. The proposed method was applied for the treatment of seven cervical cancer patients. Its effectiveness was evaluated and a correlation between the patient characteristics and the volumetric dose reduction of small bowel was also investigated. Brachytherapy treatment plans were built before and after the proposed method, and their dose-volume histograms were compared for targets and organs-at-risk. In this comparison, all plans were normalized to satisfy the same D90% for high-risk clinical target volume. RESULTS: For the enrolled patients, the average dose of small bowel was significantly reduced from 75.2 ± 4.9 Gy before to 60.2 ± 4.0 Gy after the prone position procedure, while minor dosimetric changes were observed in rectum, sigmoid and bladder. The linear correlation to body mass index, thickness and width of abdominopelvic cavity and bladder volume were 76.2, 69.7, 28.8 and -36.3%, respectively. CONCLUSIONS: The application of prone position procedure could effectively lower the volumetric dose of the small bowel. The dose reduction in the small bowel had a strong correlation with the patient's obesity and abdominal thickness. This means the patients for whom the proposed method would be beneficial can be judiciously selected for safe brachytherapy.

Deep learning method for prediction of patient-specific dose distribution in breast cancer.

BACKGROUND: Patient-specific dose prediction improves the efficiency and quality of radiation treatment planning and reduces the time required to find the optimal plan. In this study, a patient-specific dose prediction model was developed for a left-sided breast clinical case using deep learning, and its performance was compared with that of conventional knowledge-based planning using RapidPlan™. METHODS: Patient-specific dose prediction was performed using a contour image of the planning target volume (PTV) and organs at risk (OARs) with a U-net-based modified dose prediction neural network. A database of 50 volumetric modulated arc therapy (VMAT) plans for left-sided breast cancer patients was utilized to produce training and validation datasets. The dose prediction deep neural network (DpNet) feature weights of the previously learned convolution layers were applied to the test on a cohort of 10 test sets. With the same patient data set, dose prediction was performed for the 10 test sets after training in RapidPlan. The 3D dose distribution, absolute dose difference error, dose-volume histogram, 2D gamma index, and iso-dose dice similarity coefficient were used for quantitative evaluation of the dose prediction. RESULTS: The mean absolute error (MAE) and one standard deviation (SD) between the clinical and deep learning dose prediction models were 0.02 ± 0.04%, 0.01 ± 0.83%, 0.16 ± 0.82%, 0.52 ± 0.97, - 0.88 ± 1.83%, - 1.16 ± 2.58%, and - 0.97 ± 1.73% for D95%, Dmean in the PTV, and the OARs of the body, left breast, heart, left lung, and right lung, respectively, and those measured between the clinical and RapidPlan dose prediction models were 0.02 ± 0.14%, 0.87 ± 0.63%, - 0.29 ± 0.98%, 1.30 ± 0.86%, - 0.32 ± 1.10%, 0.12 ± 2.13%, and - 1.74 ± 1.79, respectively. CONCLUSIONS: In this study, a deep learning method for dose prediction was developed and was demonstrated to accurately predict patient-specific doses for left-sided breast cancer. Using the deep learning framework, the efficiency and accuracy of the dose prediction were compared to those of RapidPlan. The doses predicted by deep learning were superior to the results of the RapidPlan-generated VMAT plan.

Facial expression monitoring system for predicting patient's sudden movement during radiotherapy using deep learning.

PURPOSE: Imaging, breath-holding/gating, and fixation devices have been developed to minimize setup errors so that the prescribed dose can be exactly delivered to the target volume in radiotherapy. Despite these efforts, additional patient monitoring devices have been installed in the treatment room to view patients' whole-body movement. We developed a facial expression recognition system using deep learning with a convolutional neural network (CNN) to predict patients' advanced movement, enhancing the stability of the radiation treatment by giving warning signs to radiation therapists. MATERIALS AND METHODS: Convolutional neural network model and extended Cohn-Kanade datasets with 447 facial expressions of source images for training were used. Additionally, a user interface that can be used in the treatment control room was developed to monitor real-time patient's facial expression in the treatment room, and the entire system was constructed by installing a camera in the treatment room. To predict the possibility of patients' sudden movement, we categorized facial expressions into two groups: (a) uncomfortable expressions and (b) comfortable expressions. We assumed that the warning sign about the sudden movement was given when the uncomfortable expression was recognized. RESULTS: We have constructed the facial expression monitoring system, and the training and test accuracy were 100% and 85.6%, respectively. In 10 patients, their emotions were recognized based on their comfortable and uncomfortable expressions with 100% detection rate. The detected various emotions were represented by a heatmap and motion prediction accuracy was analyzed for each patient. CONCLUSION: We developed a system that monitors the patient's facial expressions and predicts patient's advanced movement during the treatment. It was confirmed that our patient monitoring system can be complementarily used with the existing monitoring system. This system will help in maintaining the initial setup and improving the accuracy of radiotherapy for the patients using deep learning in radiotherapy.

H5N8 Highly Pathogenic Avian Influenza in the Republic of Korea: Epidemiology During the First Wave, from January Through July 2014.

OBJECTIVES: This study describes the outbreaks of H5N8 highly pathogenic avian influenza (HPAI) in Korea during the first wave, from January 16, 2014 through July 25, 2014. Its purpose is to provide a better understanding of the epidemiology of H5N8 HPAI. METHODS: Information on the outbreak farms and HPAI positive wild birds was provided by the Animal and Plant Quarantine Agency. The epidemiological investigation sheets for the outbreak farms were examined. RESULTS: During the 7-month outbreak period (January-July 2014), H5N8 HPAI was confirmed in 212 poultry farms, 38 specimens from wild birds (stools, birds found dead or captured). Ducks were the most frequently infected poultry species (159 outbreak farms, 75.0%), and poultry in 67 (31.6%) outbreak farms was asymptomatic. CONCLUSION: As in the previous four H5N1 epidemics of HPAI that occurred in Korea, this epidemic of H5N8 proved to be associated with migratory birds. Poultry farms in Korea can hardly be free from the risk of HPAI introduced via migratory birds. The best way to overcome this geographical factor is to reinforce biosecurity to prevent exposure of farms, related people, and poultry to the pathogen.

Endovascular coil trapping of a ruptured dissecting aneurysm of the vertebral artery using detachable coils and micro-tornado® coils.

We experienced a patient with a ruptured dissecting aneurysm of the vertebral artery who was treated by trapping of the lesion using Guglielmi detachable coils (GDCs) with micro-tornado® coils (MTCs). An 80-year-old male was transferred with a ruptured left vertebral artery dissecting aneurysm (VADA). The dissected portion of the vertebral artery was effectively trapped using GDCs and MTCs. The MTCs used for neurointervention were comprised of various types of coils and we successfully placed them into the parent artery of the dissected segment. The author suggests that this case demonstrates the usefulness of endovascular coil trapping of VADAs using MTCs in achievement of embolization.

Radiological and clinical results of laminectomy and posterior stabilization for severe thoracolumbar burst fracture : surgical technique for one-stage operation.

OBJECTIVE: This study aimed to show the possibility of neural canal enlargement and restoration of bony fragments through laminectomy and minimal facetectomy without pediculectomy or an anterior approach, and also to prove the adequacy of posterior stabilization of vertebral deformities after thoracolumbar bursting fracture. METHODS: From January 2003 to June 2009, we experienced 45 patients with thoracolumbar burst fractures. All patients enrolled were presented with either a neural canal compromise of more than 40% with a Benzel-Larson Grade of VI, or more than 30% compromise with less than a Benzel-Larson Grade of V. Most important characteristic of our surgical procedure was repositioning retropulsed bone fragments using custom-designed instruments via laminectomy and minimal facetectomy without removing the fractured bone fragments. Beneath the dural sac, these custom-designed instruments could push the retropulsed bone fragments within the neural canal after the decompression and bone fragment repositioning. RESULTS: The mean kyphotic deformities measured preoperatively and at follow-up within 12 months were 17.7 degrees (±6.4 degrees) and 9.6 degrees (±5.2 degrees), respectively. The mean midsagittal diameter improved from 8.8 mm (±2.8 mm) before surgery to 14.2 mm (±1.6 mm) at follow-up. The mean traumatic vertebral body height before surgery was 41.3% (±12.6%). At follow-up assessment within 12 months, this score showed a statistically significant increase to 68.3% (±12.8%). Neurological improvement occurred in all patients. CONCLUSION: Though controversy exists in the treatment of severe thoracolumbar burst fracture, we achieved effective radiological and clinical results in the cases of burst fractures causing severe canal compromise and spinal deformity by using this novel custom-designed instruments, via posterior approach alone.

A dumbbell-shaped meningioma mimicking a schwannoma in the thoracic spine.

A 50-year-old man presented bilateral hypesthesia on and below the T6 dermatome and paresthesia. Magnetic resonance imaging (MRI) showed an intraspinal extradural tumor, which located from the 6th thoracic vertebral body to the upper margin of the 7th vertebral body, continuing dumbbell-like through the intervertebral foramen into the right middle thorax suggesting a neurogenic tumor (neurofibroma or neurilemmoma). With the patient in a prone position, we exposed and excised the tumor via a one stage posterior approach through a hemi-laminictomy of T6. Histologic examination showed a grade 1 meningothelial meningioma, according to the World Health Organization classification. Initially, we assumed the mass was a schwannoma because of its location and dumbbell shape. However, the tumor was actually a meningioma. Postoperatively, hypesthesia resolved completely and motor power of the leg gradually full recovered. A postoperative MRI revealed no evidence of residual tumor.