Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Bioaccessibility and Antioxidant Capacity of Grape Seed and Grape Skin Phenolic Compounds After Simulated In Vitro Gastrointestinal Digestion.

Grapes present recognized beneficial effects on human health due to their polyphenolic composition. The grape overproduction together with the wine sales down and the world socioeconomic situation makes the wine grape valorization a promising strategy to give an added-value to this natural product. The objective of the present work was to study the influence of in vitro gastrointestinal digestion on antioxidant capacity and polyphenolic profile of skin and seed extracts of different grape varieties (Tempranillo, Graciano, Maturana tinta and Hondarrabi zuri). After in vitro gastrointestinal digestion, total phenolic content (TPC) of seed polyphenolic extracts decreased significantly for all the varieties. The highest decrease was for Tempranillo going from 108 ± 9 to 50 ± 3 mg / g dry matter (dm). This variety also showed the highest decrease of 90% in antioxidant capacity. However, for all the skin polyphenolic extracts there was an increase in TPC. The highest variation was also for Tempranillo. It varied from 10.1 ± 0.8 to 55.1 ± 0.9 mg / g dm. Among red varieties Tempranillo skin polyphenolic extract showed the lowest undigested anthocyanin content but the highest bioaccessibility index (BI) of 77%. For flavanols, flavonols and procyanidins the seed polyphenolic extracts showed a BI at the intestinal phase between 11% for (+)-epicatechin gallate to 130% procyanidin A2. The results of this study suggest that grape skin extracts and grape seed extracts are a reliable source of bioaccessible antioxidant polyphenols, to be used for the development of antioxidant supplements with specific functionalities depending on the grape variety.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production.

Insect plagues are a problem often hard to solve due to the harmful effects caused by the pesticides used to combat them. Consequently, the pesticide market is increasingly trying to develop new technologies to prevent the unwanted effects that common plague treatments usually bring with them. In this work, four specific bioattractants of Musca domestica, extracted from fungi (ß-ocimene, phenol, p-cresol, and indole) were microencapsulated with ß-cyclodextrin in order to produce an economically and environmentally sustainable bait containing biocides in the near future. Cyclodextrins will retain these volatile compounds until their use by the consumer when the product comes into contact with water. Then, the bioattractants will be released in the medium in a controlled manner. An analytical methodology based on headspace extraction coupled to gas chromatography and mass spectrometry (HS-GC/MS) has been developed and validated following Environmental Protection Agency (EPA) and European Commission Directorate General for Health and Food Safety guidelines for the bioattractants controlled release study from the microencapsulated product. The analytical method has been shown to be accurate and precise and has the sensitivity required for controlled release studies of the four bioattractants analyzed. The release of the bioattractants from microencapsulated products achieved the "plateau" after 3 h in all cases.

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot'em all!

BACKGROUND: About 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients. MATERIALS AND METHODS: Patients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel. RESULTS: Between 2015-2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52-84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1-6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3-65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27-56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded. CONCLUSIONS: Simultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.

Optimization of XCMS parameters for LC-MS metabolomics: an assessment of automated versus manual tuning and its effect on the final results.

INTRODUCTION: Several software packages containing diverse algorithms are available for processing Liquid Chromatography-Mass Spectrometry (LC-MS) chromatographic data and within these deconvolution packages different parameters settings can lead to different outcomes. XCMS is the most widely used peak picking and deconvolution software for metabolomics, but the parameter selection can be hard for inexpert users. To solve this issue, the automatic optimization tools such as Isotopologue Parameters Optimization (IPO) can be extremely helpful. OBJECTIVES: To evaluate the suitability of IPO as a tool for XCMS parameters optimization and compare the results with those manually obtained by an exhaustive examination of the LC-MS characteristics and performance. METHODS: Raw HPLC-TOF-MS data from two types of biological samples (liver and plasma) analysed in both positive and negative electrospray ionization modes from three groups of piglets were processed with XCMS using parameters optimized following two different approaches: IPO and Manual. The outcomes were compared to determine the advantages and disadvantages of using each method. RESULTS: IPO processing produced the higher number of repeatable (%RSD < 20) and significant features for all data sets and allowed the different piglet groups to be distinguished. Nevertheless, on multivariate level, similar clustering results were obtained by Principal Component Analysis (PCA) when applied to IPO and manual matrices. CONCLUSION: IPO is a useful optimization tool that helps in choosing the appropriate parameters. It works well on data with a good LC-MS performance but the lack of such adequate data can result in unrealistic parameter settings, which might require further investigation and manual tuning. On the contrary, manual selection criteria requires deeper knowledge on LC-MS, programming language and XCMS parameter interpretation, but allows a better fine-tuning of the parameters, and thus more robust deconvolution.

Comparison of liver and plasma metabolic profiles in piglets of different ages as animal models for paediatric population.

Liver plays an important role in drug metabolism, so studying the grade of maturation of this organ would help to develop more appropriate dosing regimens for paediatric populations. Nevertheless, considering the invasive nature of liver analyses there are obvious ethical boundaries, particularly in babies and children. In this work, we investigated the suitability of blood plasma as an alternative matrix to evaluate the biological age of liver. With this aim, we studied the correlation of plasma and liver metabolomic profiles obtained by HPLC-TOF-MS for piglets of different ages (newborns, neonates and infants). By means of Pearson correlation analysis we observed that 360 and 1784 pairs of metabolite features were significantly correlated in positive and negative ionization mode, respectively. Procrustes analysis was applied in order to assess the similarity of the clustering resulting from the data obtained from the two matrices and the two ionisation modes. The Procrustes distances were low for both ESI+ (0.3753) and ESI- (0.3673) and, hence, liver and plasma are expected to provide similar discriminatory information. Furthermore, we found that Multiblock Principal Component Analysis (MB-PCA) readily allowed us to combine the data obtained from both matrices and to better understand the clustering according to the three study groups. Considering all these results, we suggest that plasma can provide valuable insight into the maturation grade of liver in order to provide accurate dosing in paediatric population.

Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS.

Dried blood spot (DBS) has lately experienced an increase in its use in bioanalysis due to its several advantages compared with traditional blood sampling methods. Nevertheless, the use of DBS with quantitative purposes is hindered by the heterogeneous distribution of some compounds in the supporting matrix and the dependence of the response on different factors, such as the hematocrit, blood volume, and sampling position. In this study the effect of those factors in the analytical response was investigated by ultra high performance liquid chromatography coupled to fluorescence detection, using amiloride and propranolol as model compounds. The results showed a heterogeneous and drug-dependent distribution of the compounds in the blood spot. While amiloride concentration was higher in the center, propranolol concentration was higher in the periphery of the spot. Besides, the influence of the hematocrit on the quantitative results was observed. MALDI mass spectrometry imaging (MALDI-IMS) has allowed study of the distribution of the two cardiovascular drugs when they were placed in the DBS card using water:methanol solutions, demonstrating that they followed a similar distribution pattern as in blood. This work has showed the potentiality of the MALDI-IMS technique to predict the distribution of the drugs in the DBS card.

Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study.

A pilot study for the investigation of the maturation grade of children has been carried out using plasma samples already analyzed in a previous pharmacokinetic study. By using a meticulous data treatment, possible confounding factors that may hinder the obtained results were identified. By doing so, it was possible to obtain enough evidence to support the feasibility of performing a larger study eluding some unwanted variability and minimizing not only the number of subjects involved but also the time and money spent on the study. In the pilot study the metabolic profiles obtained using UHPLC-TOF-MS technique of plasma samples from 14 newborn piglets (<5 days) were compared with the plasma profiles of 16 infant piglets (8 weeks). The type of anaesthesia administered, gender, vein or artery of blood extraction and time of sampling were studied as possible confounding factors. Unsupervised analysis by principal component analysis (PCA) clearly differentiated between neonates and children. During the data treatment and the statistical analysis, the effect of confounding factors such as the anaesthetic regimen was identified and removed, while the effect of the rest of studied factors was not considered relevant, and the discrimination between the two groups based on the age was maintained. This allowed extracting relevant conclusions for a future study design while avoiding the unnecessary sacrifice of animals. Furthermore, the results obtained demonstrate the utility of metabolomics in the discovery of novel putative plasma biomarkers such as carnitines that can be correlated with the maturation state of paediatric patients.

Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS.

Eight human plasma preparation protocols were evaluated for their suitability for metabolomic studies by ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry: organic solvent protein precipitation (PPT) with either methanol or acetonitrile in 2:1 and 3:1 (v/v) ratios with plasma; solid-phase extraction (SPE) using C18 or HybridSPE cartridges; and a combination of PPT and SPE C18 cartridges and microextraction by packed sorbent. A study design in which the order of injection of the samples was not randomized is presented. The analyses were conducted in a BEH C18 column (1.7 µm, 2.1 mm × 100 mm) using a linear gradient from 100% water to 100% methanol, both with 0.1% formic acid, in 21 min. The most reproducible protocol considering both the univariate and the multivariate analysis results was PPT with acetonitrile in a 2:1 (v/v) ratio with plasma, offering a mean coefficient of variation of the area of all the detected features of 0.15 and one of the best clusterings in the principal component analysis plots. On the other hand, the highest number of extracted features was achieved using methanol in a 2:1 (v/v) ratio with plasma as the PPT solvent, closely followed by the same protocol with acetonitrile in a 2:1 (v/v) ratio with plasma, which offered only 1.2% fewer repeatable features. In terms of concentration of remaining protein, protocols based on PPT with acetonitrile provided cleaner extracts than protocols based on PPT with methanol. Finally, pairwise comparison showed that the use of PPT- and SPE-based protocols offers a different coverage of the metabolome.

Moderate hypofractionated radiation therapy and pathologic response for soft tissue sarcomas (STS) of limbs and trunk: experience from a tertiary cancer center.

BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results.

Purpose: Moderate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methods: A prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: With a median follow-up of 19 months (range 1-49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. Conclusions: One-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Behaviour of Vespa velutina nigrithorax (Hymenoptera: Vespidae) under Controlled Environmental Conditions.

From its introduction in Europe, Vespa velutina nigrithorax has become an invasive species, since it is a predator of native fruits and insects, most of the latter being honeybees. Despite the knowledge on the life cycle of this hornet, Asian hornet behaviour is not well understood, since in vivo studies on this species are quite difficult to perform. In this work, an observational study of the behaviour of this invasive species in captivity has been carried out. Two secondary and one embryo nests were caught and kept under controlled environmental conditions, up to 13 weeks for the secondary nest and 6 weeks for the embryo nest. Captivity adaptation, defence against perturbations, evolution of the colony and overwintering were the different behaviours studied. The study has shown the importance of avoiding disturbances to the nest from the beginning of the experiments, since they tend to destroy the colony. The aggressive behaviour observed in the embryo nest was lower than in the secondary nests. Results of this research will allow obtaining additional information on this species, which is crucial to develop effective control methods.

Acute skin toxicity of ultra-hypofractionated whole breast radiotherapy with simultaneous integrated boost for early breast cancer.

Background: Whole-breast irradiation (WBI) after breast conserving surgery (BCS) is indicated to improve loco-regional control and survival. Former studies showed that addition of tumor bed boost in all age groups significantly improved local control although no apparent impact on overall survival but with an increased risk of worse cosmetic outcome. Even though shortened regimens in 3 weeks are considered the standard, recent studies have shown the non-inferiority of a treatment regimen of 5 fractions in one-week in both locoregional control and toxicity profile, although simultaneous integrated boost (SIB) in this setting has been scarcely studied. Materials and Methods: From March-2020 to March-2022, 383 patients with early breast cancer diagnosis and a median age of 56 years-old (range 30-99)were included in a prospective registry of ultra-hypofractionated WBI up to a total dose of 26 Gy in 5.2 Gy/fraction with a SIB of 29 Gy in 5.8 Gy/fraction in 272 patients (71%), 30-31 Gy in 6-6.2 Gy/fraction in 111 patients (29%) with close/focally affected margins. Radiation treatment was delivered by conformal 3-D technique in 366 patients (95%), VMAT in 16patients (4%) and conformal 3-D with deep inspiration breath hold (DIBH) in 4patients (1%). Ninety-three per cent of patients received endocrine therapy and 43% systemic or targeted chemotherapy. Development of acute skin complications was retrospectively reviewed. Results: With a median follow-up of 18 months (range 7-31), all patients are alive without evidence of local, regional or distant relapse. Acute tolerance was acceptable, with null o mild toxicity: 182 (48%) and 15 (4%) patients developed skin toxicity grade 1 and 2 respectively; 9 (2%) and 2 (0.5%) patients breast edema grade 1and 2 respectively. No other acute toxicities were observed. We also evaluated development of early delayed complications and observed grade 1 breast edema in 6 patients (2%); grade 1 hyperpigmentation in 20 patients (5%); and grade 1 and 2 breast induration underneath boost region in 10(3%) and 2 patients (0.5%) respectively. We found a statistically significant correlation between the median PTVWBI and presence of skin toxicity (p = 0.028) as well as a significant correlation between late hyperpigmentation with the median PTVBOOST (p = 0.007) and the ratio PTVBOOST/PTVWBI (p = 0.042). Conclusion: Ultra-hypofractionated WBI + SIB in 5 fractions over one-week is feasible and well tolerated, although longer follow-up is necessary to confirm these results.

Efficacy of Protein Baits with Fipronil to Control Vespa velutina nigrithorax (Lepeletier, 1836) in Apiaries.

The yellow-legged hornet (Vespa velutina nigrithorax), outside its natural range, has become a major threat to domestic bees. Several control methods have been used to fight against V. velutina, but the results achieved are not satisfactory. The use of protein baits with biocides has shown to be an effective method to control invasive wasp populations, but they have not been used to control V. velutina. Thus, the efficacy of protein baits containing fipronil to reduce the presence of hornets in apiaries was evaluated in this study. After laboratory determination of the optimal efficacy of a protein bait at a 0.01% concentration of fipronil, field trials were conducted involving 222 beekeepers. The data reported by the 90 beekeepers who completed the requested questionnaire demonstrated that in the groups of apiaries with the highest pressure of hornets (groups with 10-30 and >30 hornets), there was a significant decrease in the presence of V. velutina, lasting at least two weeks. The reduction in the number of hornets was positively correlated with bait consumption, and bait consumption was positively correlated with the number of hornets present at the time of treatment. Although the method used has shown good efficacy and the concentration of fipronil used was very low; possible negative effects on the environment should also be evaluated.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

Real-world efficacy of postoperative radiotherapy with a moderate dose-escalation for phyllodes tumors of the breast.

Background: Phyllodes tumors are rare breast tumors comprising less than 1% of cases, categorized as benign, borderline, or malignant. Treatment typically involves complete surgical excision with wide margins. Adjuvant radiotherapy may be recommended for borderline or malignant tumors, or when clear margins cannot be achieved through surgery alone. Methods: We conducted a retrospective review of 14 women diagnosed with phyllodes tumors between 2015 and 2023. Among them, 36% had benign tumors and 64% had borderline/malignant tumors. The majority (86%) underwent breast-conserving surgery. Postoperative radiation therapy was delivered to the whole breast/chest wall, with a median biologically effective dose (BED) of 92.7 Gy (90.0-102.6 Gy), representing a moderate dose-escalation over conventional breast cancer schedules. Results: After a median follow-up of 48.5 months, no local or distant recurrence were observed. Mild to moderate skin toxicity occurred in all patients: 36% reported grade 1, 43% grade 2, and 21% grade 3 toxicity. One patient developed grade 2 fibrosis during follow-up. No significant correlations were found between the severity of acute/late toxicity and tumor size, surgical approach, or the radiation field's planning target volume (PTV). Conclusions: Adjuvant radiation therapy appears to be well tolerated and feasible for high-risk phyllodes tumors. However, the decision to utilize radiotherapy should be personalized, considering tumor characteristics and the risks and benefits associated with treatment.

Stereotactic body radiation therapy (SBRT) for spinal metastases: 12 years of a single center experience.

OBJECTIVE: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer.

BACKGROUND: Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques. RESULTS: NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels. CONCLUSIONS: Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.