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Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. Methods and materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5–19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

We isolated and purified phenolic acids and flavonoids from the ethanolic extract of Salvia plebeia using silica gel and a Sephadex LH-20 column chromatography. Spectroscopy revealed the isolated compounds were caffeic acid, rosmarinic acid, hispidulin, luteolin, jaceosidin, nepitrin, homoplantaginin, 6-hydroxyluteolin 7-O-glucoside, 6-methoxynaringenin 7-O-glucoside, naasanone, and cosmosiin. Quantitative analyses, using high-performance liquid chromatography coupled with UV (HPLC-UV), revealed that the major flavonoid from S. plebeia was 6-hydroxyluteolin 7-O-glucoside (100.63 mg/g) and the most abundant phenolic acid was rosmarinic acid (47.73 mg/g). Furthermore, among four other Salvia species, S. officinalis contained the highest overall phenolic acid and flavonoid level but these were still lower than S. plebeia. These results can help assess the potential of phenolic acids and flavonoids as potent sources of pharmacological ingredients from different Salvia species extracts.

Abstract Backgrounds Quality of life (QoL) has become a major concern as the survival time of breast cancer increases. We investigated the changes in QoL through comprehensive categorical analysis, for the first three years after breast cancer treatment including radiotherapy. Methods A total of 1156 patients were enrolled from 17 institutions. All survivors were grouped according to a surveillance period of 9–15 months (first year), 21–27 months (second year), and 33–39 months (third year) from the end of radiotherapy. The 5-dimensional questionnaire by the EuroQol group (EQ-5D) and the EORTC Quality of Life Questionnaire; breast cancer specific module (QLQ-BR23) were checked by self-administrated method. Results First, second and third year groups comprised 51.0, 28.9, and 21.0%. In EQ-5D-3 L (3-Likert scale) analysis, pain/discomfort and anxiety/depression categories showed lower QoL. In multivariate analyses of EQ-5D-VAS (visual-analogue scale), categories of pain/discomfort and self-care were improved with time; axillary dissection was a significant clinical factor deteriorates pain/discomfort, self-care and usual activities. In QLQ-BR23 analysis, the lowest scored category was sexual activity, followed by sexual enjoyment, future perspective, and hair loss, and the best scored category was breast symptoms. In multivariate analyses, arm symptoms, breast symptoms and body image were improved with time. Conclusions Categories of pain/discomfort and self-care in EQ-5D-VAS, arm/breast symptoms and body image in QLQ-BR23 were improved, while categories of anxiety/depression and future perspective BR23 were not, suggesting necessity of psychosocial support. This research provides comprehensive information on the categorical aspects of QoL and changes during early follow-up after breast cancer treatment.

Purpose This study aimed to evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy. Materials and Methods Medical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p < 0.001, p=0.018, and p < 0.001, respectively). Other characteristics were not significantly different between the two groups. Results With a median follow-up of 95 months (range, 1 to 249 months), there were nine locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and p=0.009, respectively). Conclusion Locoregional recurrence rate was very low in node-negative breast cancer of 5 cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT. Materials and Methods This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively. Results The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3. Conclusion PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the prevalence of infections with human papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium in the semen of Korean infertile couples and their associations with sperm quality. Methods: Semen specimens were collected from 400 men who underwent a fertility evaluation. Infection with above five pathogens was assessed in each specimen. Sperm quality was compared in the pathogen-infected group and the non-infected group. Results: The infection rates of human papillomavirus, C. trachomatis, U. urealyticum, M. hominis, and M. genitalium in the study subjects were 1.57%, 0.79%, 16.80%, 4.46%, and 1.31%, respectively. The rate of morphological normality in the U. urealyticum-infected group was significantly lower than in those not infected with U. urealyticum. In a subgroup analysis of normozoospermic samples, the semen volume and the total sperm count in the pathogen-infected group were significantly lower than in the non-infected group. Conclusion: Our results suggest that infection with U. urealyticum alone and any of the five sexually transmitted infections are likely to affect sperm morphology and semen volume, respectively. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of radiotherapy (RT) in patients who underwent hysterectomy for uterine carcinosarcoma (UCS). Methods: Patients with the International Federation of Gynecology and Obstetrics stage I- IVa UCS who were treated between 1990 and 2012 were identified retrospectively in a multiinstitutional database. Of 235 identified patients, 97 (41.3%) received adjuvant RT. Twentytwo patients with a history of previous pelvic RT were analyzed separately. Survival outcomes were assessed using the Kaplan-Meier method and Cox proportional hazards model. Results: Patients with a previous history of pelvic RT had poor survival outcomes, and 72.6% of these patients experienced locoregional recurrence; however, none received RT after a diagnosis of UCS. Univariate analyses revealed that pelvic lymphadenectomy (PLND) and para-aortic lymph node sampling were significant factors for locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS). Among patients without previous pelvic RT, the percentage of locoregional failure was lower for those who received adjuvant RT than for those who did not (28.5% vs. 17.5%, p=0.107). Multivariate analysis revealed significant correlations between PLND and LRRFS, distant metastasis-free survival, and DFS. In subgroup analyses, RT significantly improved the 5-year LRRFS rate of patients who did not undergo PLND (52.7% vs. 18.7% for non-RT, p<0.001). Conclusion: Adjuvant RT decreased the risk of locoregional recurrence after hysterectomy for UCS, particularly in patients without surgical nodal staging. Given the poorer locoregional outcomes of patients previously subjected to pelvic RT, meticulous re-administration of RT might improve locoregional control while leading to less toxicity in these patients. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods: A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancer treated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion: We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to acquire information on brachytherapy resources in Korea through a national survey of radiation oncologists. Methods: Between October 2014 and January 2015, a questionnaire on the current status of brachytherapy was distributed to all 86 radiation oncology departments in Korea. The questionnaire was divided into sections querying general information on human resources, brachytherapy equipment, and suggestions for future directions of brachytherapy policy in Korea. Results: The response rate of the survey was 88.3%. The average number of radiation oncologists per center was 2.3. At the time of survey, 28 centers (36.8%) provided brachytherapy to patients. Among the 28 brachytherapy centers, 15 (53.5%) were located in in the capital Seoul and its surrounding metropolitan areas. All brachytherapy centers had a high-dose rate system using 192Ir (26 centers) or 60Co (two centers). Among the 26 centers using 192Ir sources, 11 treated fewer than 40 patients per year. In the two centers using 60Co sources, the number of patients per year was 16 and 120, respectively. The most frequently cited difficulties in performing brachytherapy were cost related. A total of 21 centers had a plan to sustain the current brachytherapy system, and four centers noted plans to upgrade their brachytherapy system. Two centers stated that they were considering discontinuation of brachytherapy due to cost burdens of radioisotope source replacement. Conclusion: The present study illustrated the current status of brachytherapy in Korea. Financial difficulties were the major barriers to the practice of brachytherapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival. Methods: The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision. Results: The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity. Conclusion: The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic factors and clinical outcomes of 56 patients with vulvar cancer treated with curative radiotherapy (RT) or concurrent chemoradiotherapy. Materials and Methods: Overall survival (OS) and disease-free survival (DFS) were assessed retrospectively. Prognostic factors evaluated included age, International Federation of Gynecology and Obstetrics (FIGO) stage, TNM classification, tumor size, treatment modality, RT duration, and RT field. The association between the tumor human papillomavirus (HPV) status and survival was analyzed in 35 patients. Results: During the median follow-up of 2.8 years (range, 0.3 to 18.9 years), 21 patients (37.5%) experienced treatment failure. Fifteen patients (27%) had local failure: nine (16%) local failure only, three (5%) locoregional failure, two (4%) local and distant failure, and one (2%) locoregional and distant failure. Of 56 patients, seven (13%) had persistent disease at the first follow-up at 2 months and all but one died within a year after completing RT. The 5-year OS and DFS were 51.6% and 44.0%, respectively. In multivariate analysis, clinical size =3 cm predicted a poor prognostic factor for DFS (p = 0.040) and age (≥70 years) was poor prognostic for DFS (p = 0.032) and OS (p = 0.048). Patients with HPV-positive tumors tended to have better 5-year OS and DFS, but the differences were not significant statistically. Conclusion: Clinical size ≥3 cm was a significant prognostic factor for DFS. However, age was the most important prognostic factor for DFS and OS in patients treated with curative RT. Further studies are needed to determine which treatment should be considered for old age ≥70 years. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy and safety of accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) multicatheter interstitial brachytherapy for early-stage breast cancer. Methods: Between 2002 and 2006, 48 prospectively selected patients with early-stage breast cancer received APBI using multicatheter brachytherapy following breast-conserving surgery. Their median age was 52 years (range 36-78). A median of 34 Gy (range 30-34) in 10 fractions given twice daily within 5 days was delivered to the tumor bed plus a 1- 2 cm margin. Most (92%) patients received adjuvant systemic treatments. The median follow-up was 53 months (range 36-95). Actuarial local control rate was estimated from surgery using Kaplan-Meier method. Results: Local recurrence occurred in two patients. Both were true recurrence/marginal miss and developed in patients with close (< 0.2 cm) surgical margin after 33 and 40 months. The 5-year actuarial local recurrence rate was 4.6%. No regional or distant relapse and death has occurred to date. Late Grade 1 or 2 late skin and subcutaneous toxicity was seen in 11 (22.9%) and 26 (54.2%) patients, respectively. The volumes receiving 100% and 150% of the prescribed dose were significantly higher in the patients with late subcutaneous toxicity (p = 0.018 and 0.034, respectively). Cosmesis was excellent to good in 89.6%. Conclusions: APBI using HDR multicatheter brachytherapy yielded local control, toxicity, and cosmesis comparable to those of conventional whole breast irradiation for select early-stage breast cancer. Patients with close resection margins may be ineligible for APBI. [ABSTRACT FROM AUTHOR]

Purpose To develop a nomogram predicting the risks of distant metastasis following postoperative adjuvant radiation therapy for early stage cervical cancer. Materials and methods We reviewed the medical records of 1069 patients from ten participating institutions. Patients were divided into two cohorts: a training set (n = 748) and a validation set (n = 321). The demographic, clinical, and pathological variables were included in the univariate Cox proportional hazards analysis. Clinically established and statistically significant prognostic variables were utilized to develop a nomogram. Results The model was constructed using four variables: histologic type, pelvic lymph node involvement, depth of stromal invasion, and parametrial invasion. This model demonstrated good calibration and discrimination, with an internally validated concordance index of 0.71 and an externally validated c-index of 0.65. Compared to FIGO staging, which showed a broad range in terms of distant metastasis, the developed nomogram can accurately predict individualized risks based on individual risk factors. Conclusions The devised model offers a significantly accurate level of prediction and discrimination. In clinical practice it could be useful for counseling patients and selecting the patient group who could benefit from more intensive/further chemotherapy, once validated in a prospective patient cohort. [ABSTRACT FROM AUTHOR]