Convolutional Neural Network-Based Automatic Segmentation of Substantia Nigra on Nigrosome and Neuromelanin Sensitive MR Images

Recently, neuromelanin and nigrosome imaging techniques have been developed to evaluate the substantia nigra in Parkinson’s disease. Previous studies have shown potential benefits of quantitative analysis of neuromelanin and nigrosome images in the substantia nigra, although visual assessments have been performed to evaluate structures in most studies. In this study, we investigate the potential of using deep learning based automatic region segmentation techniques for quantitative analysis of the substantia nigra. The deep convolutional neural network was trained to automatically segment substantia nigra regions on 3D nigrosome and neuromelanin sensitive MR images obtained from 30 subjects. With a 5-fold cross-validation, the mean calculated dice similarity coefficient between manual and deep learning was 0.70 ± 0.11. Although calculated dice similarity coefficients were relatively low due to empirically drawn margins, selected slices were overlapped for more than two slices of all subjects. Our results demonstrate that deep convolutional neural network-based method could provide reliable localization of substantia nigra regions on neuromelanin and nigrosome sensitive MR images.

Convolutional Neural Network-Based Automatic Segmentation of Substantia Nigra on Nigrosome and Neuromelanin Sensitive MR Images

Recently, neuromelanin and nigrosome imaging techniques have been developed to evaluate the substantia nigra in Parkinson’s disease. Previous studies have shown potential benefits of quantitative analysis of neuromelanin and nigrosome images in the substantia nigra, although visual assessments have been performed to evaluate structures in most studies. In this study, we investigate the potential of using deep learning based automatic region segmentation techniques for quantitative analysis of the substantia nigra. The deep convolutional neural network was trained to automatically segment substantia nigra regions on 3D nigrosome and neuromelanin sensitive MR images obtained from 30 subjects. With a 5-fold cross-validation, the mean calculated dice similarity coefficient between manual and deep learning was 0.70 ± 0.11. Although calculated dice similarity coefficients were relatively low due to empirically drawn margins, selected slices were overlapped for more than two slices of all subjects. Our results demonstrate that deep convolutional neural network-based method could provide reliable localization of substantia nigra regions on neuromelanin and nigrosome sensitive MR images.

Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy / 한국유방암학회지

Purpose@#A relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer. @*Methods@#Pre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7). @*Results@#WARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression. @*Conclusion@#Our results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.

Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy / 한국유방암학회지

Purpose@#A relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer. @*Methods@#Pre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7). @*Results@#WARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression. @*Conclusion@#Our results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.

Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. RESULTS: With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. CONCLUSION: The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED₁₀) (≥ 79.2 Gy₁₀ vs. 80 cm³; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

The factors affecting the level of urgency in the frequent users of the emergency department

OBJECTIVE@#study was conducted to identify patients who actually require medical treatment in the frequent users of the emergency department (ED) and evaluate the factors affecting the level of urgency by Korean Triage and Acuity Scale.@*METHODS@#We retrospectively reviewed the medical records of frequent users who used more than four times a year to the ED in 2015. They were triaged on every use of ED and divided into non-urgent group and urgent group based on an average triage scale of three. The characteristics were compared between both groups.@*RESULTS@#The total 443 patients were frequent users and they used the ED 2,944 times. The urgent group included 92 patients, and their median number of ED uses were 4 times. The urgent group was older and higher rate of male than the non-urgent group. The more patients suffered from medical diseases such as diabetes, cerebrovascular disease, ischemic heart disease, other heart disease, lung disease, and kidney disease in the urgent group. There was no difference in education, and socioeconomic status, and ratio uses with same symptoms in both groups. At the end of the study two years later, 55% of the urgent group died.@*CONCLUSION@#The urgent group consists of 92 patients (21%) of the frequent emergent department users. The factors affecting the level of urgency are male sex, cerebrovascular disease, other heart disease, lung disease, and kidney disease as medical history. On the other hand, the psychiatric history and other minor diseases are factors affecting reversely the level of urgency.

Tumor Volume Reduction Rate during Adaptive Radiation Therapy as a Prognosticator for Nasopharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to evaluate the prognostic significance of the tumor volume reduction rate (TVRR) measured during adaptive definitive radiation therapy (RT) for nasopharyngeal cancer (NPC). MATERIALS AND METHODS: We reviewed the RT records of 159 NPC patients treated with definitive RT with or without concurrent chemotherapy between January 2006 and February 2013. Adaptive re-planning was performed in all patients at the third week of RT. The pre- and mid-RT gross tumor volumes (GTVs) of the primary tumor and the metastatic lymph nodes were measured and analyzed for prognostic implications. RESULTS: After a median follow-up period of 41.5 months (range, 11.2 to 91.8 months) for survivors, there were 43 treatment failures. The overall survival and progression-free survival (PFS) rates at 5 years were 89.6% and 69.7%, respectively. The mean pre-RT GTV, mid-RT GTV, and TVRR were 45.9 cm3 (range, 1.5 to 185.3 cm3), 26.7 cm3 (1.0 to 113.8 cm3), and -41.9% (range, -87% to 78%), respectively. Patients without recurrence had higher TVRR than those with recurrence (44.3% in the no recurrence group vs. 34.0% in the recurrence group, p=0.004), and those with TVRR > 35% achieved a significantly higher rate of PFS at 5 years (79.2% in TVRR > 35% vs. 53.2% in TVRR ≤ 35%; p < 0.001). In multivariate analysis, TVRR was a significant factor affecting PFS (hazard ratio, 2.877; 95% confidence interval, 1.555 to 5.326; p=0.001). CONCLUSION: TVRR proved to be a significant prognostic factor in NPC patients treated with definitive RT, and could be used as a potential indicator for early therapeutic modification during the RT course.

Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2-IIIA) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%). RESULTS: During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively. CONCLUSION: Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.

Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma

PURPOSE: To investigate the outcomes of patients with spinal metastases from hepatocellular carcinoma (HCC), who were treated by stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: This retrospective study evaluated 23 patients who underwent SBRT from October 2008 to August 2012 for 36 spinal metastases from HCC. SBRT consisted of approximately 2 fractionation schedules, which were 18 to 40 Gy in 1 to 4 fractions for group A lesions (n = 15) and 50 Gy in 10 fractions for group B lesions (n = 21). RESULTS: The median follow-up period was 7 months (range, 2 to 16 months). Seven patients developed grade 1 or 2 gastrointestinal toxicity, and one developed grade 2 leucopenia. Compression fractures occurred in association with 25% of the lesions, with a median time to fracture of 2 months. Pain relief occurred in 92.3% and 68.4% of group A and B lesions, respectively. Radiologic response (complete and partial response) occurred in 80.0% and 61.9% of group A and B lesions, respectively. The estimated 1-year spinal-tumor progression-free survival rate was 78.5%. The median overall survival period and 1-year overall survival rate were 9 months (range, 2 to 16 months) and 25.7%, respectively. CONCLUSION: SBRT for spinal metastases from HCC is well tolerated and effective at providing pain relief and radiologic response. Because compression fractures develop at a high rate following SBRT for spinal metastases from primary HCC, careful follow up of the patient is required.

Negative impact of pretreatment anemia on local control after neoadjuvant chemoradiotherapy and surgery for rectal cancer

PURPOSE: Although anemia is considered to be a contributor to intra-tumoral hypoxia and tumor resistance to ionizing radiation in cancer patients, the impact of pretreatment anemia on local control after neoadjuvant concurrent chemoradiotherapy (NACRT) and surgery for rectal cancer remains unclear. MATERIALS AND METHODS: We reviewed the records of 247 patients with locally advanced rectal cancer who were treated with NACRT followed by curative-intent surgery. RESULTS: The patients with anemia before NACRT (36.0%, 89/247) achieved less pathologic complete response (pCR) than those without anemia (p = 0.012). The patients with pretreatment anemia had worse 3-year local control than those without pretreatment anemia (86.0% vs. 95.7%, p = 0.005). Multivariate analysis showed that pretreatment anemia (p = 0.035), pathologic tumor and nodal stage (p = 0.020 and 0.032, respectively) were independently significant factors for local control. CONCLUSION: Pretreatment anemia had negative impacts on pCR and local control among patients who underwent NACRT and surgery for rectal cancer. Strategies maintaining hemoglobin level within normal range could potentially be used to improve local control in rectal cancer patients.

Radiation sigmoiditis mimicking sigmoid colon cancer after radiation therapy for cervical cancer: the implications of three-dimensional image-based brachytherapy planning / 부인종양

External-beam radiation therapy with intracavitary high-dose-rate brachytherapy is the standard treatment modality for advanced cervical cancer; however, late gastrointestinal complications are a major concern after radiotherapy. While radiation proctitis is a well-known side effect and radiation oncologists make an effort to reduce it, the sigmoid colon is often neglected as an organ at risk. Herein, we report two cases of radiation sigmoiditis mimicking sigmoid colon cancer after external-beam radiation therapy with intracavitary high-dose-rate brachytherapy for uterine cervical cancer with dosimetric consideration.