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Background: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. Methods: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6–9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0–29.9%, 30–49.9%, 50–69.9%, 70–79.9%, 80–89.9%, and 90–100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. Results: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. Conclusion: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

Abstract Aim Patients with locoregionally uncontrolled breast tumors are frequently referred for breast palliative radiotherapy (PRT) to mitigate symptoms. We analyzed the outcomes following breast PRT to optimize PRT according to risk groups. Methods We reviewed 133 patients who underwent breast PRT. A median total dose of 45 Gy was prescribed with an equivalent dose in 2 Gy fractions (EQD2, α/β = 3.5) of 53 Gy. The Cox proportional hazards model was used to analyze the prognostic factors of local control (LC). Results Most (90.2%) had polymetastatic disease (> 5 lesions), and 48.9% had bone metastasis. With a median follow-up of 17.2 months, the 2-year LC and overall survival (OS) rates were 49.4%, and 48.3%, respectively. Multivariable analyses demonstrated progressive or mixed responses outside the breast and > 2 lines of previous therapy as adverse features for clinical outcomes. Group 1 (0 risk factors) showed favorable 2-year LC and OS of 63.9%, and 72.8%, respectively, whereas group 3 (2 risk factors) showed the worst outcomes of 0%, and 6.8%, respectively. Breast PRT with EQD2 ≥ 63 Gy showed a significant benefit in LC for group 1 and marginal benefit (p = 0.055) for group 2, but no improvement for group 3 (p = 0.300). Conclusion Breast PRT showed favorable LC outcomes in patients with stable disease outside the breast and treated with ≤ 2 lines of systemic treatment. Our findings warrant future clinical trials investigating the role of higher than palliative dose and early intervention of PRT in stage IV patients.

Aim: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. Methods: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. Results: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. Conclusion: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Aim: Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease. Methods: We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR. Results: With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001). Conclusion: We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.

Abstract 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.

Background: It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. Methods: We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. Results: After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). Conclusions: IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

Abstract Background Excessive skeletal muscle loss during neoadjuvant concurrent chemoradiotherapy (NACRT) is significantly related to survival outcomes of oesophageal cancer. However, the conventional method for measuring skeletal muscle mass requires computed tomography (CT) images, and the calculation process is labour‐intensive. In this study, we built machine‐learning models to predict excessive skeletal muscle loss, using only body mass index data and blood laboratory test results. Methods We randomly split the data of 232 male patients treated with NACRT for oesophageal cancer into the training (70%) and test (30%) sets for 1000 iterations. The naive random over sampling method was applied to each training set to adjust for class imbalance, and we used seven different machine‐learning algorithms to predict excessive skeletal muscle loss. We used five input variables, namely, relative change percentage in body mass index, albumin, prognostic nutritional index, neutrophil‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio over 50 days. According to our previous study results, which used the maximal χ2 method, 10.0% decrease of skeletal muscle index over 50 days was determined as the cut‐off value to define the excessive skeletal muscle loss. Results The five input variables were significantly different between the excessive and the non‐excessive muscle loss group (all P

Purpose To analyze growth patterns over 2 years after birth according to preterm infant birth weight and length percentiles. Methods Anthropometric measurements of 82 preterm infants were retrospectively reviewed. Preterm infants with birth weight or length below the 10th percentile were classified as small for gestational age (SGA) (n=19) and those between the 10th and 89th percentile as appropriate for gestational age (AGA) (n=63). The association between the length standard deviation score (SDS) at 2 years of corrected age and clinical factors were analyzed. Results The length SDS of the SGA group was significantly increased at 6 months (-1.30±1.71) and 24 months (-0.97±1.06) of corrected age. The length SDS was lower in the SGA group than those in the AGA group at 6 months (-1.30±1.71 vs. -0.25±1.15, P=0.004), 18 months (-0.97±1.39 vs. -0.03±1.29, P=0.015), and 24 months (-0.97±1.06 vs. -0.29±1.12, P=0.022,). The percentage of children with a length SDS of

Abstract Background This study aimed to determine the optimal radiotherapy (RT) regimen for patients with clinical metastasis to the internal mammary lymph node (cIMN+) from breast cancer. Methods We retrospectively reviewed the medical records of 84 patients with cIMN+ breast cancer treated with curative surgery, taxane-based chemotherapy, and postoperative RT between January 2009 and December 2014. Postoperative RT was administered to the whole breast or chest wall using 50 Gy in 2 Gy fractions. Boost RT to the internal mammary lymph node (IMN) was administered at the physician’s discretion. We categorized patients into two groups according to the IMN dose as follows: low-dose IMN RT (50.0–63.5 Gy) and high-dose IMN RT (63.6–70.4 Gy). Results After a median follow-up of 58 months (range, 12–111 months), IMN recurrence was observed in 2 patients (2.4%), and all IMN recurrences developed simultaneously with distant metastases. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 89.1, 72.0, and 81.2%, respectively. The triple-negative subtype, IMN size ≥1.0 cm, old age, and low-dose IMN were significantly associated with poor DFS. Among the patients with IMN size ≥1.0 cm, the 5-year DFS was significantly higher in those treated with high-dose IMN RT than in those treated with low-dose IMN RT (69.3% vs. 33.3%, p = 0.019). Conclusions IMN RT without IMN dissection resulted in favorable outcomes in cIMN+ breast cancer. For patients with a large IMN, a higher IMN radiation dose might be needed for disease control.

Objectives: This analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). Methods: A retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10–90% volume, and irradiated volume receiving more than 10–25 Gy (PTV_V10 – 25 Gy). Results: Among 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p

Purpose To determine the prevalence and clinical findings of benign thyroid nodules and cancer in Korean pediatric patients with thyroid nodules. Methods We investigated the medical records of 134 patients aged younger than 18 years who had a goiter, thyroid nodule, thyroid mass, or thyroid cancer who underwent fine needle aspiration biopsy (FNAB). Results The study population included 113 females (84.3%) and 21 males (13.7%); the mean patient age was 16.1±2.3 years (range, 8–18 years). Of the 134 patients, 24 (18.0%) were finally diagnosed with thyroid cancer, of which 20 (83.3%) were papillary cancer and 4 (16.7%) were follicular cancer. No patient was exposed to radiation. FNAB revealed malignant cancer in 21 of the patients; 3 were initially reported as having benign tumors by FNAB, but were later diagnosed with follicular cancer. An additional 13 patients were suspected to have malignant tumors by FNAB, with a final diagnosis of nodular hyperplasia. Cystic nodules were more common in the benign group. The percentages of cervical lymphadenopathy and irregular nodular margins were higher in the malignant group compared to the benign group. Cervical lymphadenopathy and FNAB malignant findings were highly suggestive of malignant nodules. Conclusions Thyroid cancer prevalence in a Korean pediatric population is comparable to reported estimates of worldwide thyroid cancer prevalence. In this population, cancer predominates on the right thyroid lobe. Papillary thyroid cancers are dominant in the Korean pediatric population but are less prevalent than in Korean adults. As expected, FNAB was highly accurate in predicting malignant nodules.

Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC.

Proton therapy offers a distinct physical advantage over conventional X-ray therapy, but its biological advantages remain understudied. In this study, we aimed to identify genetic factors that contribute to proton sensitivity in breast cancer (BC). Therefore, we screened relative biological effectiveness (RBE) of 230 MeV protons, compared to 6 MV X-rays, in ten human BC cell lines, including five triple-negative breast cancer (TNBC) cell lines. Clonogenic survival assays revealed a wide range of proton RBE across the BC cell lines, with one out of ten BC cell lines having an RBE significantly different from the traditional generic RBE of 1.1. An abundance of cyclin D1 was associated with proton RBE. Downregulation of RB1 by siRNA or a CDK4/6 inhibitor increased proton sensitivity but not proton RBE. Instead, the depletion of cyclin D1 increased proton RBE in two TNBC cell lines, including MDA-MB-231 and Hs578T cells. Conversely, overexpression of cyclin D1 decreased the proton RBE in cyclin D1-deficient BT-549 cells. The depletion of cyclin D1 impaired proton-induced RAD51 foci formation in MDA-MB-231 cells. Taken together, this study provides important clues about the cyclin D1-CDK4-RB1 pathway as a potential target for proton beam therapy in TNBC.

The aim of this study was to assess the anti-inflammatory and anti-apoptotic effects of KIOM-2015EW, the hot-water extract of maple leaves in hyperosmolar stress (HOS)-induced human corneal epithelial cells (HCECs). HCECs were exposed to hyperosmolar medium and exposed to KIOM-2015EW with or without the hyperosmolar media. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production and apoptosis were observed, and the activation of mitogen-activated protein kinases (MAPKs) including extracellular signal regulated kinase (ERK), p38 and c-JUN N-terminal kinase (JNK) signaling and nuclear factor (NF)-κB was confirmed. Compared to isomolar medium, the induction of cell cytotoxicity significantly increased in HCECs exposed to hyperosmolar medium in a time-dependent manner. KIOM-2015EW-treatment significantly reduced the mRNA and protein expression of pro-inflammatory mediators and apoptosis. KIOM-2015EW-treatment inhibited HOS-induced MAPK signaling activation. Additionally, the HOS-induced increase in NF-κB phosphorylation was attenuated by KIOM-2015EW. The results demonstrated that KIOM-2015EW protects the ocular surface by suppressing inflammation in dry eye disease, and suggest that KIOM-2015EW may be used to treat several ocular surface diseases where inflammation plays a key role.

Purpose: There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities. Materials and Methods: Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed. Results: A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies. Conclusion Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed. [ABSTRACT FROM AUTHOR]

Purpose Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. Materials and Methods A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. Results The radiation oncologists chose "bone" more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored "peritoneal seeding" (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that "irrelevant, if all metastatic lesions are amendable to local therapy", while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. Conclusion This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD. [ABSTRACT FROM AUTHOR]

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist's and surgeon's perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested. [ABSTRACT FROM AUTHOR]