Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

External validation of subclassification system and progression pattern analysis in hepatocelluar carcinoma with macroscopic vascular invasion.

BACKGROUND AND PURPOSE: The present study aimed to validate the performance of a previously proposed subclassification model to predict prognosis after combined transarterial chemoembolization (TACE) and external beam radiotherapy (RT) for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) in an independent cohort that received the same first-line treatment for the patients with the similar disease extent characteristics, and analyzed the progression patterns as well as progression-free survival (PFS). MATERIALS AND METHODS: This study was conducted using prospectively collected data from the XXXXX HCC registry for newly diagnosed, previously untreated HCC between 2005 and 2018. Finally, 417 patients who satisfied the eligibility criteria were included and analyzed. RESULTS: The median PFS and overall survival (OS) were 5.2 and 13.9 months, respectively. Similar to a previous study, subclassification of patients into very low-, low-, intermediate-, and high-risk groups showed a median OS of 98.4, 18.3, 9.7, and 5.8 months, respectively (P < 0.001). Additionally, subclassification of patients into the very low-, low-, intermediate-, and high-risk groups showed median PFS of 18.7, 6.7, 3.3, and 2.3 months, respectively (p < 0.001). Overall, intrahepatic progression was the most common pattern of progression; however, extrahepatic progression was more common in the intermediate- and high-risk groups. CONCLUSION: The previously proposed subclassification model was successfully validated in an independent cohort. Treatment modification should be considered in the intermediate- and high-risk patient groups because of their frequent extrahepatic as well as intrahepatic progressions after combined TACE and RT.

Waiting Time for Breast Cancer Treatment in Korea: A Nationwide Cohort Study.

PURPOSE: This study aimed to analyze the waiting time for initial treatment after breast cancer diagnosis and determine the factors influencing treatment delay in South Korea. METHODS: This nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment data. The participants were classified according to the regions where their biopsy and treatment were performed (Seoul-Seoul, Metro-Metro, Other-Other, Metro-Seoul, Other-Seoul). Waiting time was analyzed according to regional subgroup, year of diagnosis, and type of treatment. Multivariable logistic regression models were constructed to identify the factors associated with treatment delay (after 30 days of diagnosis). RESULTS: A total of 133,514 participants newly diagnosed between January 2010 and December 2017 were included in the study. The median waiting time for initial treatment in the total population increased from 8 days, in 2010, to 14 days, in 2017. In the Seoul-Seoul group, the waiting time increased from 10 days, in 2010, to 16 days, in 2017. Although the median waiting time was approximately 10 days in the Metro-Metro and Other-Other groups, it was 27 and 24 days, in the Metro-Seoul and Other-Seoul group, respectively, in 2017. The proportion of delayed upfront surgery by more than 30 days was higher in the Metro-Seoul (odds ratio [OR], 8.088; 95% confidence interval [CI], 7.357-8.893; p < 0.001) and Other-Seoul (OR, 6.210; 95% CI, 5.717-6.750; p < 0.001) groups than in the Metro-Metro (OR, 1.468; 95% CI, 1.352-1.594; p < 0.001) and Other-Other (reference) groups. Previous medical history and treatment at tertiary hospital were observed as factors related to delayed surgery. CONCLUSION: Waiting times for breast cancer surgery have increased across all regions of Korea, with those traveling to Seoul experiencing particularly long wait times.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment.

Background/Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0-4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions: Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Domestic medical travel from non-Seoul regions to Seoul for initial breast cancer treatment: a nationwide cohort study.

Purpose: This study was conducted to investigate the trend of domestic medical travel from non-Seoul areas to Seoul for initial breast cancer treatment, and identify factors associated with medical travel in breast cancer patients. Methods: A nationwide retrospective cohort study was performed using the Health Insurance Review and Assessment data of South Korea. Patients were classified according to the regions in which they underwent breast biopsy (Seoul vs. metropolitan cities vs. other regions). Frequencies of biopsy, diagnosis, treatment, and domestic medical travel were analyzed according to regions, and factors associated with medical travel were investigated. Results: A total of 150,709 breast cancer survivors who were diagnosed between January 2010 and December 2017 were included. The total rate of medical travel from non-Seoul regions to Seoul had increased from 14.2% (1,161 of 8,150) in 2010 to 19.8% (2,762 of 13,964) in 2017. Approximately a quarter of patients from other regions traveled to Seoul, and over 40% of patients from Chungbuk, Gyeongbuk, and Jeju regions traveled to Seoul for initial treatment in 2017. The difference in the annual frequencies of upfront surgery between Seoul and non-Seoul regions increased over time. Younger age and regions other than metropolitan cities were significantly related to medical travel. Patients covered by medical aid or past medical histories were significantly less likely to travel to Seoul for initial breast cancer treatment. Conclusion: Medical travel to Seoul for upfront breast cancer surgery is increasing. Policies for appropriate healthcare delivery need to be established in the near future.

A study of quantitative indicators for slice sorting in cine-mode 4DCT.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Radiologic Response as a Prognostic Factor in Advanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion after Transarterial Chemoembolization and Radiotherapy.

Introduction: We evaluated the radiologic response rate of combined transarterial chemoembolization (TACE) plus radiotherapy (RT) in treatment-naïve patients with liver-confined hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI) and analyzed its clinical importance in overall survival (OS) outcomes. Methods: Patients who were treated with TACE plus RT as a first-line treatment for HCC with MVI between January 2010 and December 2015 were retrospectively reviewed. Radiologic response was assessed according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 2 and 4 months after completion of RT. Landmark analysis at 2 and 4 months, and time-dependent Cox regression analysis using response as a time-dependent covariate were performed for univariable and multivariable analyses. Results: The 2-month landmark analysis included 427 patients, and the 4-month landmark analysis included 355 patients after excluding patients without imaging studies for response evaluation at 4 months. Radiologic responses were observed in 210 (49.2%) patients at 2 months and 181 (51.8%) patients at 4 months. In multivariable analyses, radiologic response was identified as an independent prognosticator for OS at 2 months (median OS: responders, 23.1 months vs. nonresponders, 8.0 months; hazard ratio [HR], 3.194; p < 0.001) and 4 months (median OS: responders, 26.5 months vs. nonresponders, 9.3 months; HR, 4.534; p < 0.001). Conclusion: Radiologic response assessed by mRECIST was a significant prognostic factor for OS in patients with advanced-stage HCC showing MVI treated with combined TACE plus RT.

Stereotactic Body Radiation Therapy versus Concurrent Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Propensity Score-Matched Analysis.

In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (n = 95) or CCRT (n = 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3-64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%, p = 0.455), PFS (40.0% vs. 54.2%, p = 0.123), and FFLP (77.2% and 87.1%, p = 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.

Radiation-induced C-reactive protein triggers apoptosis of vascular smooth muscle cells through ROS interfering with the STAT3/Ref-1 complex.

Damage to normal tissue can occur over a long period after cancer radiotherapy. Free radical by radiation can initiate or accelerate chronic inflammation, which can lead to atherosclerosis. However, the underlying mechanisms remain unclear. Vascular smooth muscle cells (VSMCs) proliferate in response to JAK/STAT3 signalling. C-reactive protein (CRP) can induce VSMCs apoptosis via triggering NADPH oxidase (NOX). Apoptotic VSMCs promote instability and inflammation of atherosclerotic lesions. Herein, we identified a VSMCs that switched from proliferation to apoptosis through was enhanced by radiation-induced CRP. NOX inhibition using lentiviral sh-p22phox prevented apoptosis upon radiation-induced CRP. CRP overexpression reduced the amount of STAT3/Ref-1 complex, decreased JAK/STAT phosphorylation and formed a new complex of Ref-1/CRP in VSMC. Apoptosis of VSMCs was further increased by CRP co-overexpressed with Ref-1. Functional inhibition of NOX or p53 also prevented apoptotic activity of the CRP-Ref-1 complex. Immunofluorescence showed co-localization of CRP, Ref-1 and p53 with α-actin-positive VSMC in human atherosclerotic plaques. In conclusion, radiation-induced CRP increased the VSMCs apoptosis through Ref-1, which dissociated the STAT3/Ref-1 complex, interfered with JAK/STAT3 activity, and interacted with CRP-Ref-1, thus resulting in transcription-independent cell death via p53. Targeting CRP as a vascular side effect of radiotherapy could be exploited to improve curability.

Stereotactic body radiation therapy as a salvage treatment for single viable hepatocellular carcinoma at the site of incomplete transarterial chemoembolization: a retrospective analysis of 302 patients.

BACKGROUND: To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE). METHODS: Patients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10-15 Gy per fraction were given over 3-4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03. RESULTS: A total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6-41.7) and the median tumor size was 2.0 cm (range, 0.7-6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9-4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field. CONCLUSION: SBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.

Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study.

Background/Aim: We aimed to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) in elderly patients with small hepatocellular carcinomas (HCC). Methods: Eighty-three patients (89 lesions) with HCC who underwent SBRT between January 2012 and December 2018 were reviewed in this retrospective observational study. The key inclusion criteria were as follows: 1) age ≥75 years, 2) contraindications for hepatic resection or percutaneous ablative therapies, 3) no macroscopic vascular invasion, and 4) no extrahepatic metastasis. Results: The patients were 75-90 years of age, and 49 (59.0%) of them were male. Most patients (94.0%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Seventy-four patients (89.2%) had Child-Pugh class A hepatic function before SBRT. The median tumor size was 1.6 cm (range, 0.7-3.5). The overall median follow-up period was 34.8 months (range, 7.3-99.3). The 5-year local tumor control rate was 90.1%. The 3-year and 5-year overall survival rate was 57.1% and 40.7%, respectively. Acute toxicity grade ≥3 was observed in three patients (3.6%) with elevated serum hepatic enzymes; however, no patient experienced a worsening of the Child-Pugh score to ≥2 after SBRT. None of the patients developed late toxicity (grade ≥3). Conclusions: SBRT is a safe treatment option with a high local control rate in elderly patients with small HCC who are not eligible for other curative treatments.

Oncologic outcomes of immediate breast reconstruction in young women with breast cancer receiving neoadjuvant chemotherapy.

BACKGROUND: Oncologic safety of postmastectomy breast reconstruction in young women with breast cancer is not well-defined, especially in the setting of neoadjuvant chemotherapy (NACT). We retrospectively compared the oncologic outcomes following nipple-sparing (NSM)/skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) and conventional mastectomy (CM) alone in young breast cancer patients after NACT. METHODS: A total of 1266 women with primary breast cancer who underwent NACT followed by total mastectomy with or without IBR were reviewed. Of these, only young patients (age ≤ 40 years at diagnosis) were included in the outcome analysis (n = 375). After propensity score-matching by clinical T and N stage, molecular subtype, response to NACT, and adjuvant radiotherapy status, 228 patients were 1:1 matched, comprising balanced IBR group (with NSM/SSM) and CM-alone group. RESULTS: The 5-year locoregional recurrence-free, disease-free, distant metastasis (DM)-free, and breast cancer-specific survival (BCSS) rates for the entire cohort of young patients were 83.4%, 65.3%, 71.7%, and 85.4%, respectively. Locoregional recurrence rates between the matched groups were similar (14% vs. 15.8%; p = 0.710); however, IBR group had significantly lower DM rate (27.2% vs. 40.4%; p = 0.036) and breast cancer mortality (14.9% vs. 27.2%; p = 0.023) than CM-alone group. IBR group showed significantly improved 5-year DM-free survival (74.1% vs. 62.6%; p = 0.043) and BCSS (89.1% vs. 77.6%; p = 0.048) rates than CM-alone group. CONCLUSIONS: Our results indicated that IBR with NSM/SSM does not negatively affect long-term oncologic outcomes compared to CM alone in young women with breast cancer receiving NACT.

Radiofrequency Ablation versus Stereotactic Body Radiation Therapy in the Treatment of Colorectal Cancer Liver Metastases.

PURPOSE: This study aimed to compare the treatment outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) for colorectal cancer liver metastases (CRLM) and to determine the favorable treatment modality according to tumor characteristics. MATERIALS AND METHODS: We retrospectively analyzed the records of 222 colorectal cancer patients with 330 CRLM who underwent RFA (268 tumors in 178 patients) or SBRT (62 tumors in 44 patients) between 2007 and 2014. Kaplan-Meier method and Cox models were used by adjusting with inverse probability of treatment weighting (IPTW). RESULTS: The median follow-up duration was 30.5 months. The median tumor size was significantly smaller in the RFA group than in the SBRT group (1.5 cm vs 2.3 cm, p<0.001). In IPTW-adjusted analysis, difference in treatment modality was not associated with significant differences in 1-year and 3-year recurrence-free survival (35% vs 43%, 22% vs 23%; p=0.198), overall survival (96% vs 91%, 58% vs 56%; p=0.508), and freedom from local progression (FFLP; 90% vs 72%, 78% vs 60%; p=0.106). Significant interaction effect between the treatment modality and tumor size was observed for FFLP (p=0.001). In IPTW-adjusted subgroup analysis of patients with tumor size >2 cm, the SBRT group had a higher FFLP compared with the RFA group (HR, 0.153; p<0.001). CONCLUSION: SBRT and RFA showed similar local control in the treatment of patients with CRLM. Tumor size was an independent prognostic factor for local control and SBRT may be preferred for larger tumors.

Postmastectomy Radiation Therapy for Node-Negative Breast Cancer of 5 cm or Larger Tumors: A Multicenter Retrospective Analysis (KROG 20-03).

PURPOSE: 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, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups. RESULTS: With a median follow-up of 95 months (range, 1-249), there were 9 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 0.009, respectively). CONCLUSION: Locoregional recurrence rate was very low in node-negative breast cancer of 5cm 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.

Real-world data analysis of patients with cancer of unknown primary.

Cancer of unknown primary (CUP) is a heterogeneous malignancy in which the primary site of the tumor cannot be identified through standard work-up. The survival outcome of CUP is generally poor, and there is no consensus for treatment. Here, we comprehensively analyzed the real-world data of 218 patients with CUP (median age, 62 years [range, 19-91]; male, 62.3%). Next-generation sequencing was conducted in 22 (10%) patients, one of whom showed level 1 genetic alteration. Most (60.3%) patients were treated with empirical cytotoxic chemotherapy, and two patients received targeted therapy based on the NGS results. The median OS was 8.3 months (95% confidence interval [CI] 6.2-11.4), and the median progression-free survival of patients treated with chemotherapy was 4.4 months (95% CI 3.4-5.3). In multivariate Cox regression analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 and localized disease were significantly associated with favorable survival outcomes. Collectively, we found that CUP patients had a poor prognosis after standard treatment, and those with localized disease who received local treatment and those with better PS treated with multiple lines of chemotherapy had better survival outcomes. Targeted therapies based on NGS results are expected to improve survival outcomes.

Safety and efficacy of 10-fraction hypofractionated radiation therapy for non-small cell lung cancer.

PURPOSE: To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution. MATERIALS AND METHODS: From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50-70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities. RESULTS: The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3-5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity. CONCLUSION: HFRT with 50-70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.

Evaluation of deep learning-based autosegmentation in breast cancer radiotherapy.

PURPOSE: To study the performance of a proposed deep learning-based autocontouring system in delineating organs at risk (OARs) in breast radiotherapy with a group of experts. METHODS: Eleven experts from two institutions delineated nine OARs in 10 cases of adjuvant radiotherapy after breast-conserving surgery. Autocontours were then provided to the experts for correction. Overall, 110 manual contours, 110 corrected autocontours, and 10 autocontours of each type of OAR were analyzed. The Dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to compare the degree of agreement between the best manual contour (chosen by an independent expert committee) and each autocontour, corrected autocontour, and manual contour. Higher DSCs and lower HDs indicated a better geometric overlap. The amount of time reduction using the autocontouring system was examined. User satisfaction was evaluated using a survey. RESULTS: Manual contours, corrected autocontours, and autocontours had a similar accuracy in the average DSC value (0.88 vs. 0.90 vs. 0.90). The accuracy of autocontours ranked the second place, based on DSCs, and the first place, based on HDs among the manual contours. Interphysician variations among the experts were reduced in corrected autocontours, compared to variations in manual contours (DSC: 0.89-0.90 vs. 0.87-0.90; HD: 4.3-5.8 mm vs. 5.3-7.6 mm). Among the manual delineations, the breast contours had the largest variations, which improved most significantly with the autocontouring system. The total mean times for nine OARs were 37 min for manual contours and 6 min for corrected autocontours. The results of the survey revealed good user satisfaction. CONCLUSIONS: The autocontouring system had a similar performance in OARs as that of the experts' manual contouring. This system can be valuable in improving the quality of breast radiotherapy and reducing interphysician variability in clinical practice.

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study.

BACKGROUND: Although the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea. METHODS: A nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan-Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model. RESULTS: Between 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person-years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185-11.613], 50-59 years (HR, 4.343; 95% CI, 2.122-8.891), and 40-49 years (HR, 2.121; 95% CI, 1.068-4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person-years (PY); HR, 12.460; 95% CI, 2.698-57.522] and aged 40-49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966-18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more. CONCLUSION: Young breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

Radiation therapy for recurrent extrahepatic bile duct cancer.

PURPOSE: More than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment modality has been established. We therefore analyzed our experience on the survival outcomes of radiation therapy (RT) for recurrent extrahepatic bile duct cancer (EHBDC). PATIENTS AND METHODS: We retrospectively analyzed the records of patients with recurrent EHBDC who underwent concurrent chemoradiation therapy (CCRT) or RT alone at our institution between January 2001 and June 2015. Freedom from locoregional progression (FFLP), progression-free survival (PFS), and overall survival (OS) were assessed, and univariate and multivariate analyses were performed to identify the prognostic factors. RESULTS: A total of 76 patients were included in the analysis. The median OS was 16 months and the rates of 2-year FFLP, PFS, and OS were 61%, 25%, and 33%, respectively. Among the evaluable patients, the first site of failure was the locoregional area in 16 patients, distant metastasis in 27, and both sites in 8. On univariate analysis, disease-free interval (p = 0.012) and concurrent chemotherapy (p = 0.040) were found as significant prognostic factors for OS. One patient with CCRT developed a grade 3 hematologic toxicity, and two patients experienced late grade 3 toxicities including duodenal ulcer bleeding and obstruction. CONCLUSIONS: RT for recurrent EHBDC showed favorable survival and local control with limited treatment-related toxicities. Considering that the most common pattern of failure was distant metastasis, further studies on the optimal scheme of chemotherapy and RT are warranted.

Prognostic value of the 21-gene recurrence score for regional recurrence in patients with estrogen receptor-positive breast cancer.

PURPOSE: To evaluate the prognostic value of the 21-gene recurrence score (RS) for regional recurrence (RR) in patients with estrogen receptor-positive breast cancer. METHODS: We reviewed the medical records of 446 patients who underwent 21-gene RS assay after breast-conserving surgery or mastectomy. The high-RS group was defined as patients who were (1) older than 50 years with an RS of 26 or higher, or (2) 50 years or younger with an RS of 16 or higher. RESULTS: The 5-year rates of local recurrence (LR), RR, and distant metastasis (DM) were 2.2%, 2.7%, and 4.7%, respectively. The 5-year overall survival (OS) rate was 99.1%. Of the patients, 269 (60.3%) had low-RS, while 177 (39.7%) had high-RS. The 5-year OS rate of the high-RS group was significantly lower than that of the low-RS. The 5-year rates of RR and DM in the high-RS group were significantly higher than those in the low-RS group, while the LR rates did not differ significantly. In multivariable analysis, the high-RS group had a significant relationship with increased RR rate (p = 0.037). Patients who had both high-RS and clinical high-risk features had a significantly higher 5-year RR rate (7.9%) compared with other groups. CONCLUSIONS: High-RS was an independent risk factor for RR. The significantly higher RR rate of patients with both high-RS and clinical high-risk features compared with other groups suggests that this patient group can be a potential candidate for regional nodal irradiation.