Biochemical control in intermediate- and high-risk prostate cancer after EBRT with and without brachytherapy boost.

PURPOSE: External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. METHODS: Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥ 76 Gy EQD2 (α/ß = 1.5 Gy) for IR and ≥ 78 Gy EQD2 (α/ß = 1.5 Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. RESULTS: Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49 and 51 months for HR and IR, respectively. BTB patients with ≥ 113 Gy EQD2Gy experienced a stable, good BC outcome compared with BTB at lower doses. Patients treated with ≥ 113 Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥ 113 Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5 and 20.8% for IR). CONCLUSIONS: In patients with IR and HR prostate cancer, BTB with ≥ 113 Gy EQD2Gy offered a BC advantage compared with dose-escalated EBRT and lower BTB doses.

Next-Generation Sequencing-Based Analysis of Clinical and Pathological Features of PIK3CA-Mutated Breast Cancer.

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients.

Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients.

BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy.

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

Does Production of Clarias gariepinus × Heterobranchus longifilis Hybrids Influence Quality Attributes of Fillets?

The increase in fish and seafood consumption observed in recent years is a consequence of the growing consumers' awareness of proper nutrition. One of the possibilities to provide fish-friendly, qualitatively attractive (both in terms of nutrition and sensory quality) raw fish materials is the production of hybrids, which would improve production rates without compromising their meat quality. This study compares the carcass and fillet yields of Clarias gariepinus (C) and heteroclarias C. gariepinus × Heterobranchus longifilis (H), and the nutritional (chemical composition, fat quality) and culinary quality (structure, texture, color, cooking loss, sensory characteristics) of their meat. Significantly (p ≤ 0.05) higher carcass and fillet yield was shown for H, whose fillets had comparable sensory quality and proximal composition to C. The meat of H can be an attractive raw material for more demanding groups of consumers-for children and adolescents (due to the less intense fish tastiness), as well as for older people who have problems with chewing and digesting food (due to lower sensory chewiness and perception of connective tissue).

Impact of climate-driven temperature increase on inland aquaculture: Application to land-based production of common carp (Cyprinus carpio L.).

Climate change will expose the food-producing sector to a range of challenges. Inland aquaculture farms are particularly vulnerable, due to the difficulty in changing their location, and therefore require specific tools to predict the influence of direct and indirect effects on production, environment and economic feasibility. The objective of our study was to apply a simple set of models to produce a set of growth, risk and suitability maps for stakeholders within the common carp sector in Poland, to assist decision-making under two different scenarios of climate change: a moderate situation (RCP 4.5) and an extreme situation (RCP 8.5). We used present (2000-2019) and future projections (2080-2099) for water surface temperature based on land surface temperature data from regionally downscaled climate models to draw maps to: (i) show optimal temperature conditions for carp growth, (ii) assess risk of disease outbreak caused by three important common carp pathogens: Cyprinid herpesvirus 3 (CyHV-3), carp oedema virus (CEV) and spring viremia of carp (SVCV) and (iii) predict potential suitability changes of carp farming in Poland. The study identified areas with the most and least favourable temperature conditions for carp growth, as well as those areas with the highest/lowest number of days with suitable temperatures for virus infection. These suitability maps showed the combined effect of direct and indirect effects of climate change projections under RCP 8.5 and RCP 4.5 scenarios. The approach applied herein will be of use worldwide for analysing the risks of temperature increase to land-based aquaculture, and the results presented are important for carp farmers in Poland and elsewhere, industry in general, and government stakeholders, to understand the direct and indirect effects of climate change on the triple bottom line of people, planet, and profit.

Human papillomavirus infection predicts a better survival rate in patients with oropharyngeal cancer.

INTRODUCTION: Squamous cell carcinoma is the most common malignant tumour occurring in the head and neck region. It is now understood that (human papillomavirus (HPV)- positive and HPV-negative diseases are two very different clinical entities associated with different outcomes. We decided to assess p16 expression status in patients with oropharyngeal cancer and retrospectively evaluate the outcomes of the treatment. MATERIAL AND METHODS: The evaluated group consisted of 98 consecutive patients with squamous cell carcinoma of the oropharynx treated in a combined way in Holycross Cancer Centre in Kielce in 2006-2014. For all patients p16 status was assessed based on the biological material. In 51 patients HPV infection was diagnosed. The Kaplan-Meier method was used to produce survival curves using the log-rank test and the Cox proportional hazard model was used to determine the risk factors. The following risk factors were included: HPV status (positive, negative), sex, age, smoking, histopathological grade of the tumour, clinical stage, and systemic therapy application. For HPV-positive and HPV-negative patients independent analyses were done including aforementioned factors, excluding HPV status. RESULTS: The observation time for HPV-positive patients was significantly longer (p = 0.0008). Fifty-eight patients died, 40 patients are alive. Number of deaths in HPV-negative patients was statistically significantly higher (p = 0.0222). A statistically significant difference in the disease-free survival probability and overall survival probability between HPV-positive and HPV-negative patients was found (p = 0.0045 and p = 0.0037 respectively). For disease-free survival a statistically significant factor of the risk of recurrence was HPV infection (p = 0.0169). For HPV-positive patients, age (p = 0.0199) and smoking (p = 0.0353) were statistically significant risk factors of recurrence. For HPV-negative patients significant risk factors of recurrence were clinical stage (p = 0.0114) and systemic therapy application (p = 0.0271). For overall survival for the entire group statistically significant risk factors were absence of HPV infection (p = 0.0123), male sex (p = 0.0426), and age (p = 0.0311). For HPV-positive patients, age (p = 0.0096) and smoking (p = 0.0387) were statistically significant risk factors of death. For HPV-negative patients significant risk factors of death were clinical stage (p = 0.0120) and systemic therapy application (p = 0.0460). CONCLUSIONS: Our data show that HPV infection is a predictor of better disease-free and overall survival in patients with oropharyngeal cancer. For HPV-positive oropharyngeal cancer patients weekly given cisplatin with concurrent radiotherapy can be an alternative to three weekly given cisplatin considering effectiveness and early toxicity.

Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy.

PURPOSE: Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. METHODS AND MATERIALS: This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. RESULTS: Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity. CONCLUSIONS: Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

Effects of steaming on health-valuable nutrients from fortified farmed fish: Gilthead seabream (Sparus aurata) and common carp (Cyprinus carpio) as case studies.

Fish fortification with iodine-rich macroalgae (Laminaria digitata) and Selenium-rich yeast is expected to promote nutritional added value of this crucial food item, contributing to a healthy and balanced diet for consumers. However, it is not known if steaming can affect these nutrient levels in fortified fish. The present study evaluates the effect of steaming on nutrients contents in fortified farmed gilthead seabream (Sparus aurata) and common carp (Cyprinus carpio). Fortified seabream presented enhanced I, Se and Fe contents, whereas fortified carp presented enhanced I, Se and Zn contents. Steaming resulted in increased I and Se contents in fortified seabream, and increased Fe and Zn levels in fortified carp, with higher elements true retention values (TRVs >90%). The consumption of 150 g of steamed fortified seabream contributes to a significant daily intake (DI) of I (up to 12%) and Se (up to >100%). On the other hand, steamed fortified carp contributes to 19-23% of I DI and 30%-71% of Se DI. These results demonstrate that steaming is a healthy cooking method, maintaining the enhanced nutritional quality of fortified fish. Moreover, the present fortification strategy is a promising solution to develop high-quality farmed fish products to overcome nutritional deficiencies.

Structural and molecular indices in common carp (Cyprinus carpio L.) fed n-3 PUFA enriched diet.

Sustainable freshwater aquaculture has been recently gaining attention owing to the potential of nourishing the world. The study aimed to evaluate the influence of finishing diets on the activity of 21 genes involved in hepatic lipid metabolism and intestinal homeostasis, liver and intestine histology, and the level of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in common carp fillets. We compared two experimental diets: control diet mimicking a commercial feed (CTRL) and a test diet (CB) fortified with EPA and DHA retrieved from salmon by-products. An additional control (eCTRL) from extensively cultured carps was investigated. The study revealed that the expression of seven hepatic genes, e.g., lipoprotein lipase and fatty acid synthase, and six intestinal genes e.g., claudin-3c and γ-glutamyl transpeptidase, was influenced specifically by the experimental diets and farming type. Fish from the eCTRL group had the smallest hepatocytes and the largest nuclei compared with CTRL and CB. No pathological signs were found in intestine samples. Additionally, the levels of EPA and DHA in fillets were significantly higher in fish receiving CB compared with CTRL and eCTRL. The use of fortified diets is a promising solution to produce freshwater species with enhanced nutritional value without compromising the safety of fillets.

Enriched feeds with iodine and selenium from natural and sustainable sources to modulate farmed gilthead seabream (Sparus aurata) and common carp (Cyprinus carpio) fillets elemental nutritional value.

Developing tailor-made fortified farmed fish is a promising solution to overcome nutritional deficiencies and increase consumer confidence in these products. This study evaluated the supplementation of three fortified diets with I-rich seaweed and selenised-yeast on essential and toxic elements levels in gilthead seabream (Sparus aurata) and common carp (Cyprinus carpio). Fortified diets resulted in increased I, Se and Fe in fish muscle. Biofortified seabream and carp revealed lower Cu and Br. The reduction of fishmeal and fish oil in fortified diets resulted in lower Hg and Cd in seabream muscle. Contrarily, fortified diets increased As and Hg in carp fillets. The consumption of 150 g of fortified seabream enabled a significantly higher contribution to the daily recommended intake (DRI) of I (10%) and Se (76%) than non-fortified fish, whereas fortified carp fulfilled 23% of I DRI and 91% of Se DRI. Moreover, the exposure to Pb decreased with the consumption of biofortified seabream (23-82% BMDL01) and carp (26-92% BMDL01). These results support the strategy of developing eco-innovative biofortified farmed fish using sustainable, natural, safe and high-quality ingredients in feeds, to enable consumers to overcome nutritional deficiencies without significantly increased feed costs.

Relationship between inflammatory markers and clinical patterns of atrial fibrillation in patients with congestive heart failure.

BACKGROUND: Occurence of atrial fibrillation (AF) adversely affects left atrial size and cardiac function. This arrhythmia is also associated with an increase of plasma CRP and fibrinogen concentration. It is not clear whether elevated levels of inflammatory markers in patients with congestive heart failure (CHF) are associated with AF, clinical symptoms or adverse cardiac remodelling. AIM: To investigate the association between levels of inflammatory markers and selected clinical and echocardiographic parameters as well as used treatment in the population of CHF patients with various forms of AF. METHODS: The cross-sectional study included 99 patients with CHF divided into 3 groups. Group I included patients with sinus rhythm. Group II consisted of patients admitted to hospital with AF and discharged with sinus rhythm (the category of paroxysmal and persistent AF). Group III comprised patients with permanent AF. In all patients plasma CRP and fibrinogen concentrations were measured and echocardiographic examination was carried out. Left atrial dimension (LA), ejection fraction (LVEF) and right ventricular systolic pressure (RVSP) were assessed. RESULTS: Mean CRP concentration in group III (5.83+/-5.36 mg/l) was significantly higher than in group I (p=0.001) and group II (p=0.033). In the group with permanent AF mean fibrinogen concentration was elevated to a higher level (391.0+/-77.3 mg/dl) than in group II (p=0.007) and group I (p=0.099). Mean LA and RV dimensions and RVSP in group III were significantly higher than in group I and group II. Multivariable analysis revealed that plasma CRP concentration was significantly associated with the presence of arterial hypertension (p <0.001) and LA enlargement (p=0.007). A significant association between fibrinogen level and CRP level (p=0.038), presence of permanent AF (p=0.045) and metabolic syndrome (p <0.05) was found. Values of ln CRP were significantly correlated with LA diameter (r=0.24; p=0.015). CONCLUSIONS: Increased plasma CRP level in patients with CHF were significantly associated with arterial hypertension and LA enlargement. Permanent form of AF and CRP level have been shown to be significantly associated with increased plasma fibrinogen concentration in the course of CHF.