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PURPOSE/OBJECTIVE(S) Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity. MATERIALS/METHODS From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity. RESULTS In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013). CONCLUSION There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

Background and objectives The prevalence of both atrial fibrillation (AF) and cancer are increasing especially in the elderly. The occurrence of AF in cancer may be related to comorbidities of patients, cancer treatment, or a direct tumor effect. The objectives of this study were to investigate the incidence of AF according to cancer type. Methods From the Korean National Health Insurance Service elderly (NHIS-elderly) cohort (age >60), we identified 67,077 patients with newly diagnosed cancer and without previous AF. Incidence rates of new onset AF were evaluated. Results The mean age of the cancer patients was 75.1 year and 53.5% were males. During a median follow-up period of 25 months, the incidence rate of AF among overall cancer patients was higher than that of age-sex matched non-cancer population (1.42 vs. 0.69 per 100 person-years, respectively). Compared with solid cancer, the risk of incident AF in patients with hematologic cancer was significantly higher (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 1.39–1.72, p Conclusions Cancer was associated with an increased incidence of AF. Hematologic cancer was associated with higher risk of AF incidence than solid cancer. Among solid cancer, thoracic and breast cancer was most strongly associated with the risk of AF incidence. Funding Acknowledgement Type of funding source: None

Background and objectives Non-vitamin K antagonist oral anticoagulants (NOACs) are an effective and safe alternative to warfarin in atrial fibrillation (AF) patients, but there is not enough evidence that NOACs can offer sufficient protection in AF patients concomitantly diagnosed with antiphospholipid syndrome (APS). Use of rivaroxaban has been associated with an increased risk of thrombotic events compared with warfarin in results of the TRAPS trial, but the TRAPS trial is not for AF patients and included only very high-risk APS patients with triple-positive for all 3 antiphospholipid antibodies. We sought to compare thromboembolic events, bleeding, and mortality between NOAC and warfarin in patients with both AF and APS. Methods From the Korean National Health Insurance Service (NHIS) database during the period from January 1, 2011 to December 31, 2016, we identified an warfarin-treated group of patients with AF and APS (n=1,237) who were compared with a 1:1 propensity-matched NOAC treated group (n=1,237). Results After a median follow-up period of 17 months, NOAC-treated patients had lower incidence rates for ischemic stroke (5.9 and 10.5 events per 100 person-years for the NOAC and warfarin groups), major bleeding (4.1 and 8.3 events per 100 person-years, respectively), and all-cause mortality (3.4 and 15.6 events per 100 person-years, respectively) compared with warfarin in patients with AF and APS. Compared with warfarin, NOAC significantly decreased the risk of ischemic stroke (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.47–0.77, p Conclusions Compared with warfarin, AF patients with APS on NOACs had lower ischemic stroke, major bleeding, and all-cause mortality. Our data suggest that AF patients with APS can be safely and effectively treated with NOACs. Funding Acknowledgement Type of funding source: None

PURPOSE/OBJECTIVE(S) CPAP is a novel method to avoid heart radiation exposure during radiation therapy, recently proposed as an alternative to the current standard-of-care deep inspiration breath-hold technique. In this study, the heart dose, inter- and intrafraction motions in CPAP-based treatment were investigated. MATERIALS/METHODS A retrospective study on heart dose level and CPAP compliance included 237 left-sided breast cancer patients treated with CPAP-based VMAT in hypofractionation (with (n = 116) and without (n = 105) internal mammary node irradiation (IMNI)) between June 2020 and January 2021. During simulation, CT was obtained with free breathing (FB) and CPAP. For each treatment fraction, CBCT was acquired to confirm geometric accuracy within 3 mm tolerance. Two different datasets were used for reproducibility evaluations. Dataset 1: interfraction reproducibility was evaluated by measuring heart-to-PTV distance (MinHD), defined as the minimum distance between the line posteriorly tangential to the PTV and the heart, on 300 CBCT and 20 planning CT data of 20 women. Using dataset 1, heart-sparing effect was further explored by comparing dosimetric metrics of the whole heart and its substructures (e.g., atrium, ventricles, and vessels) between CPAP- and FB-based VMAT plans. Dataset 2: intrafraction reproducibility was evaluated in 20 women who were treated for different malignancies and underwent 4D CT with CPAP. RESULTS Among 237 patients recruited, the CPAP compliance was 93% with a mean heart dose of 1.6 ± 0.7 Gy (no IMNI, 1.1 Gy; IMNI 2.0 Gy). The use of CPAP during treatment did not require additional time resource. The analysis of dataset 1 (i.e., total of 300 CBCT and 20 planning CT images) showed small variations of MinHD (0.6 ± 0.2 cm), demonstrating a reasonable agreement of the heart-to-PTV distance between the planning CT and CBCTs (MinHD difference < 0.2 cm, on average, for all patients). Compared with FB, the use of CPAP significantly reduced the mean heart dose (2.1 to 1.7 Gy), the mean dose to the left ventricle, the maximum dose to the left anterior descending artery, and the mean lung dose by 21%, 23%, 36%, and 23%, respectively. In dataset 2, the breast surface motion amplitude was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm across the patients in the mediolateral, craniocaudal, and anteroposterior directions, respectively, and exceeded 5 mm for only two patients. CONCLUSION To the best of our knowledge, this is the first and largest study to evaluate the heart-sparing capability and reproducibility of CPAP-based VMAT for left-sided breast cancer treatment. A large population study confirmed a reasonably low irradiation to the heart with CPAP. This heart-sparing effect can be consistent across treatment fractions as demonstrated in sub-centimeter reproducibility of the heart position. For most of the women, the intrafraction breast motion with CPAP was minimal.

Background Cytokine genotypes have previously been studied in patients undergoing solid organ transplantation; certain polymorphisms have been implicated in the development of acute rejection (AR) and graft dysfunction (GD). Allograft outcomes determined, in part, by alloimmune responses is mainly mediated by T-cell responses, activated and driven by cytokines. Interleukin-4 (IL-4) is one such cytokine, which exerts its biological effects through binding to the IL-4 receptor (IL-4R) complex on target cells. In the present study, we investigated whether polymorphisms of the IL-4 and/or IL-4R gene were associated with susceptibility to acute AR and GD after kidney transplantation. Methods We analyzed 2 single nucleotide polymorphism (SNPs) of IL-4 (rs2243250 and rs2070874) and 3 SNPs of IL-4R (rs1801275, rs2107356, and rs1805010) in 344 kidney transplant recipients. These patients included 62 of whom had developed AR and 215 of whom had GD in 1 year after kidney transplantation. Results The AR group included 62 patients (45 men and 17 women). There was a statistically significant difference in the male-to-female ratio and the use of tacrolimus in the AR group. The GD group included 215 patients. Patients who developed GD were more likely to be older and have an underlying cause of end-stage renal disease that was unknown compared with patients who did not have GD, the cause of which was typically known. Among the SNPs examined, 1 of the SNPs in the IL-4R gene (ie, rs1801275) showed a statistical association with AR (co-dominant model, P = .061; dominant model, P = .019; and log-addictive model, P = .029). In addition, 1 of the IL-4R SNPs (ie, rs2107356) was statistically associated with GD (dominant model, P = .034). No significant difference in the IL-4 genotype was observed between the AR/GD and non-AR/non-GD subjects. Conclusions One IL-4R gene polymorphism (rs1801275) was associated with AR. In addition, a separate IL-4R SNP (rs2107356) was statistically associated with GD after kidney transplantation.

Bone morphogenetic proteins (BMP) belong to the transforming growth factor beta superfamily of proteins. This study was performed to evaluate the association of BMP gene polymorphisms with acute renal allograft rejection (AR) and graft dysfunction (GD) in Koreans.Three hundred thirty-one patients who had kidney transplantation procedures were recruited. Transplantation outcomes were determined in terms of AR and GD criteria. We selected six single nucleotide polymorphisms (SNPs): rs1979855 (5' near gene), rs1049007 (Ser87Ser), rs235767 (intron), rs1005464 (intron), rs235768 (Arg190Ser), and rs3178250 (3; untranslated region).Among the six SNPs tested, the rs235767, rs1005464, and rs3178250 SNPs were significantly associated with AR (P .05). The rs1049007 and rs235768 SNPs also showed an association with GD (P .05).In conclusion, these results suggest that the BMP2 gene polymorphism may be related to the development of AR and GD in kidney transplant recipients.

In the present study, the chemical constituents of Artemisia fukudo essential oil (AFE) were investigated using GC-MS. The major constituents were alpha-thujone (48.28%), beta-thujone (12.69%), camphor (6.95%) and caryophyllene (6.01%). We also examined the effects of AFE on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR tests indicated that AFE has potent dose-dependent inhibitory effects on pro-inflammatory cytokines and mediators. We investigated the mechanism by which AFE inhibits NO and PGE(2) by examining the level of nuclear factor-kappaB (NF-kappaB) activation within the mitogen-activated protein kinase (MAPK) pathway, which is an inflammation-induced signal pathway in RAW 264.7 cells. AFE inhibited LPS-induced ERK, JNK, and p38 phosphorylation. Furthermore, AFE inhibited the LPS-induced phosphorylation and degradation of Ikappa-B-alpha, which is required for the nuclear translocations of the p50 and p65 NF-kappaB subunits in RAW 264.7 cells. Our results suggest that AFE might exert an anti-inflammatory effect by inhibiting the expression of pro-inflammatory cytokines. Such an effect is mediated by a blocking of NF-kappaB activation which consequently inhibits the generation of inflammatory mediators in RAW264.7 cells. AFE may be useful for treating inflammatory diseases.