Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus.

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

Evaluation of Unity 1.5 T MR-linac plan quality in patients with prostate cancer.

The Unity magnetic resonance (MR) linear accelerator (MRL) with MR-guided adaptive radiotherapy (MRgART) is capable of online MRgART where images are acquired on the treatment day and the radiation treatment plan is immediately replanned and performed. We evaluated the MRgART plan quality and plan reproducibility of the Unity MRL in patients with prostate cancer. There were five low- or moderate-risk and five high-risk patients who received 36.25 Gy or 40 Gy, respectively in five fractions. All patients underwent simulation magnetic resonance imaging (MRI) and five online adaptive MRI. We created plans for 5, 7, 9, 16, and 20 beams and for 60, 100, and 150 segments. We evaluated the target and organ doses for different number of beams and segments, respectively. Variation in dose constraint between the simulation plan and online adaptive plan was measured for each patient to assess plan reproducibility. The plan quality improved with the increasing number of beams. However, the proportion of significantly improved dose constraints decreased as the number of beams increased. For some dose parameters, there were statistically significant differences between 60 and 100 segments, and 100 and 150 segments. The plan of five beams exhibited limited reproducibility. The number of segments had minimal impact on plan reproducibility, but 60 segments sometimes failed to meet dose constraints for online adaptive plan. The optimization and delivery time increased with the number of beams and segments. We do not recommend using five or fewer beams for a reproducible and high-quality plan in the Unity MRL. In addition, many number of segments and beams may help meet dose constraints during online adaptive plan. Treatment with the Unity MRL should be performed with the appropriate number of beams and segments to achieve a good balance among plan quality, delivery time, and optimization time.

Development of a prediction model for head and neck volume reduction by clinical factors, dose-volume histogram parameters and radiomics in head and neck cancer†.

In external radiotherapy of head and neck (HN) cancers, the reduction of irradiation accuracy due to HN volume reduction often causes a problem. Adaptive radiotherapy (ART) can effectively solve this problem; however, its application to all cases is impractical because of cost and time. Therefore, finding priority cases is essential. This study aimed to predict patients with HN cancers are more likely to need ART based on a quantitative measure of large HN volume reduction and evaluate model accuracy. The study included 172 cases of patients with HN cancer who received external irradiation. The HN volume was calculated using cone-beam computed tomography (CT) for irradiation-guided radiotherapy for all treatment fractions and classified into two groups: cases with a large reduction in the HN volume and cases without a large reduction. Radiomic features were extracted from the primary gross tumor volume (GTV) and nodal GTV of the planning CT. To develop the prediction model, four feature selection methods and two machine-learning algorithms were tested. Predictive performance was evaluated by the area under the curve (AUC), accuracy, sensitivity and specificity. Predictive performance was the highest for the random forest, with an AUC of 0.662. Furthermore, its accuracy, sensitivity and specificity were 0.692, 0.700 and 0.813, respectively. Selected features included radiomic features of the primary GTV, human papillomavirus in oropharyngeal cancer and the implementation of chemotherapy; thus, these features might be related to HN volume change. Our model suggested the potential to predict ART requirements based on HN volume reduction .

Dwell Time Prolongation and Identification of Single Nucleotides Passing through a Solid-State Nanopore by Using Ammonium Sulfate Aqueous Solution.

The ionic current blockades when poly(dT)60 or dNTPs passed through SiN nanopores in an aqueous solution containing (NH4)2SO4 were investigated. The dwell time of poly(dT)60 in the nanopores in an aqueous solution containing (NH4)2SO4 was significantly longer compared to that in an aqueous solution that did not contain (NH4)2SO4. This dwell time prolongation effect due to the aqueous solution containing (NH4)2SO4 was also confirmed when dCTP passed through the nanopores. In addition, when the nanopores were fabricated via dielectric breakdown in the aqueous solution containing (NH4)2SO4, the dwell time prolongation effect for dCTP still occurred even after the aqueous solution was displaced with the aqueous solution without (NH4)2SO4. Furthermore, we measured the ionic current blockades when the four types of dNTPs passed through the same nanopore, and the four types of dNTPs could be statistically identified according to their current blockade values.

Effects of one hour daily outdoor access on lying and sleeping postures, and immune traits of tethered cows.

OBJECTIVE: We investigated the effects of outdoor access for 1 h per day on the animal welfare (AW) of tethered cows, in terms of lying and sleeping postures, and immune function. METHODS: A total of five dry cows were tethered all day indoors (tethering) for 30 days and then tethered indoors with 1 h daily outdoor access (ODA-1h) for 30 days. To analyze the effects of ODA-1h, we calculated the total duration and bout frequency per day, and bout duration of lying and sleeping postures during the last five days of each treatment period. We also analyzed the populations of T cells, B cells, and NK cells in peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorting and determined the concanavalin A (Con A) -induced proliferation rate of T cells. RESULTS: The mean total time per day of lying during the ODA-1h treatment was significantly shorter than that during the tethering treatment (p<0.001). The Con A-induced proliferation rate of T cells during the ODA-1h treatment was significantly higher than that during the tethering treatment (p = 0.007). The proportion of NK cells in PBMC during the ODA-1h treatment tended to be higher than that during the tethering treatment (p = 0.062). CONCLUSION: Although ODA-1h may decrease lying time, it increases the available space for tethered cows towards that typically found in grazing and free barn feeding systems. This increased available space promotes the expression of normal behaviors such as walking and social behaviors except lying and may also improve the immune function of tethered dry cows, thereby improving their overall welfare.

Cardiac impacts of postoperative radiotherapy for breast cancer in Japanese patients.

Radiotherapy for breast cancer has attracted attention in Western countries because radiation to the heart can cause cardiac events. The purposes of this study were to evaluate the relationship between radiotherapy after breast-conserving surgery and the frequency of cardiac events in Japanese patients and to investigate the risk factors of cardiac events after postoperative radiotherapy in those patients. Female patients who received postoperative radiotherapy following breast-conserving surgery between 2007 and 2012 at our hospital were evaluated. In this study, we estimated the cumulative incidence of cardiac events including angina pectoris, myocardial infarction, ischemic heart disease, heart failure and cardiomyopathy after radiotherapy. Of 311 eligible patients, 7.1% of the patients had a smoking history, 20.3% of the patients were obese and 22.2% of the patients had hypertension. The median follow-up period was 118 months (interquartile range, 102-132 months). Twelve patients (3.9%) experienced cardiac events after treatment. The mean time to cardiac events was 126 months. The 10-year cumulative incidences of cardiac events after treatment were 4.2% and 4.3% for patients with left-sided and right-sided breast cancer, respectively, without a significant difference. Multivariate analysis showed that only hypertension was a risk factor for cardiac events (hazard ratio = 16.67, P = 0.0003). In conclusion, postoperative radiotherapy for breast cancer did not increase the incidence of cardiac events. Since at least 2007, postoperative radiotherapy for breast cancer has been safely performed without effects on the heart.

Development of a collapsed cone convolution/superposition dose calculation algorithm with a mass density-specific water kernel for magnetic resonance-guided radiotherapy.

This study aimed to develop and validate a collapsed cone convolution for magnetic resonance-guided radiotherapy (CCCMR). The 3D energy deposition kernels (EDKs) were generated in water in a 1.5-T transverse magnetic field. The CCCMR corrects the inhomogeneity in simulation geometry by referring to the EDKs according to the mass density between the interaction and energy deposition points in addition to density scaling. Dose distributions in a water phantom and in slab phantoms with inserted inhomogeneities were calculated using the Monte Carlo (MC) and CCCMR. The percentage depth dose (PDD) and off-axis ratio (OAR) were compared, and the gamma passing rate (3%/2 mm) was evaluated. The CCCMR simulated asymmetric dose distributions in the simulation phantoms, especially the water phantom, and all PDD and OAR profiles were in good agreement with the findings of the MC. The gamma passing rates were >99% for each field size and for the entire region. In the inhomogeneity phantoms, although the CCCMR underestimated dose in the low mass density regions, it could reconstruct dose changes at mass density boundaries. The gamma passing rate for the entire region was >95% for the field size of 2 × 2 cm2, but it was 68.9-86.7% for the field sizes of ≥5 × 5 cm2. Conclusively, in water, the CCCMR can obtain dose distributions comparable to those with the MC. Although the dose differences between them were mainly in inhomogeneity regions, the possibility of the effective use of the CCCMR in small field sizes was demonstrated.

Meat the challenge: Segmentation and profiling of Japanese beef mince and its substitutes consumers.

Shifts in protein production methods are an emerging challenge toward realizing a sustainable society. This paper aims to examine preferences among Japanese consumers regarding attributes of beef mince and its substitutes, to develop consumer segments based on these preferences, and to explore the segment with higher acceptance of replacement from conventional products. This paper also aims to explain intersegment differences from consumer heterogeneity in human values, scientific literacy, and sociodemographic viewpoints for a deeper understanding of consumer behavior in each segment. The results of an online choice experiment involving 4421 consumers in Japan, using food labels on mince showed that Japanese-origin organic beef was associated with the highest utility among the five production methods mentioned. Five consumer segments were identified with latent class analysis: novelty accepters, generous customers, attribute-economy balancers, price-conscious, and conservatives, which vary in preference in choice behavior, sociodemographic, human values, and scientific literacy.

Effects of music exposure during pregnancy on maternal behavior in mother rats.

Several studies have demonstrated the possibility of positive effects of exposure to music during pregnancy on mental function in humans and animals. Although there remains a core belief in the positive effects of music during pregnancy, the underlying neurobehavioral mechanisms of these effects remain unknown. In this study, we aimed to clarify the relationship between maternal nurturing behavior and the oxytocinergic system to elucidate the effect of music on mental health during pregnancy in an experimental investigation using animal models. Pregnant rats were exposed to Mozart sonatas, and their nurturing behavior after delivery was assessed using behavioral analyses. The neural activities of the oxytocinergic system, which are associated with nurturing behavior, were investigated using FosB immunohistochemistry. Music during pregnancy significantly increased the licking behavior of mothers towards pups, which is representative of positive nurturing behavior. In contrast, this alteration in maternal behavior was shown to have no marked effect on the structure or activity of the oxytocinergic system. This study provided possible evidence that exposure to music during pregnancy had a positive effect on postnatal maternal behavior. The results also suggest that the oxytocinergic system, considered a strong candidate for the neural system that regulates maternal behavior, may not be associated with this behavioral change. Understanding the relationship between other neural systems, physiological responses, and nurturing behaviors will provide a more comprehensive explanation of the mechanisms by which music exposure during pregnancy has a positive effect on mental health.

[Robot-Assisted Laparoscopic Radical Prostatectomy in a Short-Statured Man : A Case Report].

A 72-year-old man, who was extremely short-statured, underwent robot-assisted laparoscopic prostatectomy (RARP) for treatment of localized prostate cancer (cT1cNOMO). We report a case of congenital vertebral tip dysplasia with type II collagen dysplasia in a patient who underwent robot-assisted radical prostatectomy. Congenital vertebral tip dysplasia is characterized by short stature, and in this case, the height was 130 cm, which was equivalent to that of an 8-year-old child. The pelvic floor is narrow in short-statured individuals; therefore, the operative time tends to be longer than that required for routine surgery. However, using modifications in port positions and other adjustments, we performed RARP, and our perioperative results were similar to those obtained with routine RARPs.

Relationship Between Leukotriene Receptor Antagonists on Cancer Development in Patients With Bronchial Asthma: A Retrospective Analysis.

BACKGROUND/AIM: An association between leukotriene receptor antagonists (LTRA) and cancer has been previously reported, but the relationship between LTRA use and cancer prevention remains controversial. This study aimed to clarify the cancer-preventive effect of LTRA in Japanese patients with bronchial asthma. PATIENTS AND METHODS: We obtained information from a large populationbased medical information database to analyze data on patients who were newly diagnosed with bronchial asthma between 2006 and 2015. Eligible participants were patients who were prescribed an LTRA for at least 30 days (LTRA users) and those who were not using LTRA (LTRA non-users) during the objective period. LTRA users and LTRA non-users were matched 1:1 using propensity scores. RESULTS: The 1:1 propensity score matching of LTRA users and LTRA nonusers facilitated the inclusion of 3,744 participants each, in these two subgroups. The results of the Cox proportional hazards model after adjustment for covariates showed no significant difference in the cancer risk between LTRA users and non-users [adjusted hazard ratio (HR)=0.83, 95% confidence interval (CI)=0.59-1.16]. The subgroup analysis showed no significant difference in the cancer risk between the LTRA low-cumulative dose group and LTRA non-users, or between the LTRA medium-cumulative dose group and LTRA non-users. In contrast, the LTRA high-cumulative dose group had a significantly lower risk of developing cancer compared with LTRA non-users (adjusted HR=0.57, 95% CI=0.33-0.98). CONCLUSION: LTRA use may prevent cancer in patients with bronchial asthma.

Effect of different cow floor mat on the pressure in anterior knees of Holstein dry cows determined using pressure measurement sheet.

To analyze limb pain in tethered dairy cows, we compared three cow floor mat materials (pasture mat® [PM], KKM rubber mat® [RM], and woodchip [WC]) with soil ground considering the pressure applied to the anterior knee of Holstein cows. Three Holstein dry cows (791.3 ± 44.6 kg, 3.8 ± 1.1 years old) moored at the Education and Research Center of Alpine Field Science of the Faculty of Agriculture, Shinshu University, were tested. Pressure applied to the anterior knee of the cow by four different floor mat materials was compared using a commercially available pressure measurement sheet. The sustained pressures applied to the anterior knee of the test cow were 7.2 ± 1. 5, 29.3 ± 5.1, 17.0 ± 1.4, and 27.7 ± 2.5 MPa in the control, RM, PM, and WC, respectively, showing significant lower values (P < 0.05) than in the control. Sustained pressure was significantly lower in the PM than in the other treatments (P < 0.05). The RM was 41.7% cheaper than the PM. The pressure applied to the anterior knee of cow is lower on PM than on RM and WC. PM was more costly than RM but the sustained pressure was much lower on PM.

A deep learning-based radiomics approach to predict head and neck tumor regression for adaptive radiotherapy.

Early regression-the regression in tumor volume during the initial phase of radiotherapy (approximately 2 weeks after treatment initiation)-is a common occurrence during radiotherapy. This rapid radiation-induced tumor regression may alter target coordinates, necessitating adaptive radiotherapy (ART). We developed a deep learning-based radiomics (DLR) approach to predict early head and neck tumor regression and thereby facilitate ART. Primary gross tumor volume (GTVp) was monitored in 96 patients and nodal GTV (GTVn) in 79 patients during treatment. All patients underwent two computed tomography (CT) scans: one before the start of radiotherapy for initial planning and one during radiotherapy for boost planning. Patients were assigned to regression and nonregression groups according to their median tumor regression rate (ΔGTV/treatment day from initial to boost CT scan). We input a GTV image into the convolutional neural network model, which was pretrained using natural image datasets, via transfer learning. The deep features were extracted from the last fully connected layer. To clarify the prognostic power of the deep features, machine learning models were trained. The models then predicted the regression and nonregression of GTVp and GTVn and evaluated the predictive performance by 0.632 + bootstrap area under the curve (AUC). Predictive performance for GTVp regression was highest using the InceptionResNetv2 model (mean AUC = 0.75) and that for GTVn was highest using NASNetLarge (mean AUC = 0.73). Both models outperformed the handcrafted radiomics features (mean AUC = 0.63 for GTVp and 0.61 for GTVn) or clinical factors (0.64 and 0.67, respectively). DLR may facilitate ART for improved radiation side-effects and target coverage.

A Novel Staining Method for Detection of Brain Perivascular Injuries Induced by Nanoparticle: Periodic Acid-Schiff and Immunohistochemical Double-Staining.

Background: To protect developing brain from any unfavorable effects, it is necessary to construct experimental techniques that can sensitively detect and evaluate developmental toxicity. We have previously shown that brain perivascular tissues, especially perivascular macrophages (PVMs), respond sensitively even to weak stimuli by foreign toxicants such as low-dose exposure to nanoparticle. This paper shows the protocol of a novel staining method that enables easy detection and rapid evaluation of brain perivascular abnormalities. Methods: As weak stimulus, low-dose of carbon black nanoparticle (95 µg/kg) or titanium dioxide nanoparticle (100 µg/kg) was intranasally administered to pregnant mice at gestational days 5 and 9. The offspring brains were used to confirm the properties of PVMs and to find suitable protocols for the detection and evaluation of the mild denaturation of PVMs. Furthermore, various procedures of novel combinational double staining including periodic acid-Schiff (PAS) staining and immunohistochemistry were examined. In addition, we checked the alterations in neurotransmitter levels and the behaviors of the offspring. Results and discussion: Maternal exposure to low-dose of nanoparticle at levels where no significant effects on the brain were observed, such as abnormal behavior, alteration of neurotransmitter levels, or microglial activation, resulted in mild denaturation of the PVMs, which was captured by PAS staining. However, it was difficult to detect and determine slight histopathological alterations. Therefore, we established PAS-immunohistochemical double-staining method for the brain. This double staining method enabled easy detection and rapid evaluation of brain perivascular abnormalities and the relationship between PVMs and the surrounding cells. In addition, this double staining allows evaluation of the histopathological denaturation of the PVMs and the associated abnormalities in the surrounding tissues in the same section. Conclusion: The slight responses of brain perivascular tissues, such as mild denaturation of PVMs, were sensitively and easily determined by the PAS-immunohistochemical double-staining method. This double staining method is a powerful tool to assess brain perivascular injuries including PVM denaturation and the relationship between the expression of various molecules and the morphology of PVMs. We propose that the observation of the tissue around brain blood vessels using the double staining provides potential endpoints to evaluate developmental neurotoxicity.

Effects of starvation-induced negative energy balance on endoplasmic reticulum stress in the liver of cows.

OBJECTIVE: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. METHODS: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), ß-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. RESULTS: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. CONCLUSION: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.

Evaluation of the electron transport algorithm in magnetic field in EGS5 Monte Carlo code.

PURPOSE: To evaluate the accuracy of electron transport in the magnetic field of Electron Gamma Shower version 5 (EGS5) by using the special Fano cavity test. METHODS: To simulate electron transport in the magnetic field, the trajectory of the electron was reconstructed with a short step length to restrict fractional energy loss, and the maximum user step length (mxustep) was set at 0.01 cm or 0.001 cm. For the special Fano cavity test, three-layer slab Fano test geometry was used, and uniform and isotropic per unit mass mono-energetic electrons with 0.01, 0.1, 1.0, and 10 MeV were permitted from the central axis of geometry in 0.35 T and 1.5 T. Furthermore, the magnetic field strength was scaled based on the mass density of the material. The relative difference between the calculated dose to gap and the theoretical value was evaluated. Furthermore, the special Fano cavity test was also performed using EGSnrc with the electron-enhanced electric and magnetic field macros under the same conditions, and the results were compared with those of EGS5. RESULTS: Deviations in 0.35 T were within 0.3% regardless of the parameter settings. In 1.5 T, stable results within 0.3% were obtained using 0.001 cm as the mxustep, except for one at 10 MeV. Further, the accuracy of EGSnrc was within 0.2%, except for 10 MeV for a 0.2-cm gap in 1.5 T. CONCLUSIONS: EGS5 with the appropriate parameter settings enable electron transport in magnetic fields similar with the accuracy of EGSnrc.

Leukotriene Receptor Antagonist Use and Dementia Risk in Patients With Asthma: A Retrospective Cohort Study.

BACKGROUND/AIM: Recent experimental studies have reported that leukotriene receptor antagonists (LTRAs) might protect against dementia. However, few clinical studies have examined this in humans. This study assessed whether the use of LTRAs can prevent the onset of dementia in humans. PATIENTS AND METHODS: A large population-based retrospective cohort study was conducted using a health insurance claims database in Japan, which included patients newly diagnosed with bronchial asthma between 2006 and 2015. Each of these patients that was LTRA user was matched with a randomly selected LTRA non-user according to age, sex, and bronchial asthma diagnostic year. RESULTS: There were 10,471 patients in both the LTRA user and the LTRA non-user group. Using Cox proportional hazards models, a significant reduction in the risk of developing dementia was observed in the LTRA user group compared to the non-user group (adjusted hazard ratio=0.42, 95% confidence interval=0.20-0.87, p=0.019). CONCLUSION: Our data suggest that the use of LTRAs may prevent the onset of dementia in asthmatic patients.

Evaluation of performance of pelvic CT-MR deformable image registration using two software programs.

We assessed the accuracy of deformable image registration (DIR) accuracy between CT and MR images using an open-source software (Elastix, from Utrecht Medical Center) and a commercial software (Velocity AI Ver. 3.2.0 from Varian Medical Systems, Palo Alto, CA, USA) software. Five male patients' pelvic regions were studied using publicly available CT, T1-weighted (T1w) MR, and T2-weighted (T2w) MR images. In the cost function of the Elastix, we used six DIR parameter settings with different regularization weights (Elastix0, Elastix0.01, Elastix0.1, Elastix1, Elastix10, and Elastix100). We used MR Corrected Deformable algorithm for Velocity AI. The Dice similarity coefficient (DSC) and mean distance to agreement (MDA) for the prostate, bladder, rectum and left and right femoral heads were used to evaluate DIR accuracy. Except for the bladder, most algorithms produced good DSC and MDA results for all organs. In our study, the mean DSCs for the bladder ranged from 0.75 to 0.88 (CT-T1w) and from 0.72 to 0.76 (CT-T2w). Similarly, the mean MDA ranges were 2.4 to 4.9 mm (CT-T1w), 4.6 to 5.3 mm (CT-T2w). For the Elastix, CT-T1w was outperformed CT-T2w for both DSCs and MDAs at Elastix0, Elastix0.01, and Elastix0.1. In the case of Velocity AI, no significant differences in DSC and MDA of all organs were observed. This implied that the DIR accuracy of CT and MR images might differ depending on the sequence used.

Clinical predictors of severe late urinary toxicity after curative intensity-modulated radiation therapy for localized prostate cancer.

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76-80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4-210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department.