A multicenter high-quality data registry for advanced proton therapy approaches: the POWER registry.

BACKGROUND: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. METHODS: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

Reirradiation of head and neck squamous cell carcinomas: a pragmatic approach-part I: prognostic factors and indications to treatment.

INTRODUCTION: Reirradiation (reRT) of locally recurrent/second primary tumors of the head and neck region is a potentially curative treatment for patients not candidate to salvage surgery. Aim of the present study is to summarize available literature on both prognostic factors and indications to curative reRT in this clinical setting. MATERIALS AND METHODS: A narrative review of the literature was performed on two topics: (1) patients' selection according to prognostic factors and (2) dosimetric feasibility of reRT. Postoperative reRT and palliative intent treatments were out of the scope of this work. RESULTS: Patient-tumor and treatment-related prognostic factors were analyzed, together with dosimetric parameters concerning target volume and organs at risk. Based on available evidence, a stepwise approach has been proposed aiming to provide a useful tool to identify suitable candidates for curative reRT in clinical practice. This was then applied to two clinical cases, proposed at the end of this work. CONCLUSION: A second course of RT in head and neck recurrence/second primary tumors is a personalized approach that can be offered to selected patients only in centers with expertise and dedicated equipment following a multidisciplinary team discussion.

Post-operative KEloids iRradiation (POKER): does the surgery/high-dose interventional radiotherapy association make a winning hand?

PURPOSE: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule. PATIENTS AND METHODS: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)-12 Gy in 4 fractions (3 Gy/fr) twice a day-and follow-up period ≥ 24 months. RESULTS: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25-103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2-28.5) and 23.8% (95% CI 14.9-31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79-17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05-23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08-36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71-21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14-68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence. CONCLUSIONS: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection.

Multi-omics integrative modelling for stereotactic body radiotherapy in early-stage non-small cell lung cancer: clinical trial protocol of the MONDRIAN study.

BACKGROUND: Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics. METHODS: MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building. DISCUSSION: Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients. TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov (NCT05974475).

Quo vadis Radiomics? Bibliometric analysis of 10-year Radiomics journey.

OBJECTIVES: Radiomics is the high-throughput extraction of mineable and-possibly-reproducible quantitative imaging features from medical imaging. The aim of this work is to perform an unbiased bibliometric analysis on Radiomics 10 years after the first work became available, to highlight its status, pitfalls, and growing interest. METHODS: Scopus database was used to investigate all the available English manuscripts about Radiomics. R Bibliometrix package was used for data analysis: a cumulative analysis of document categories, authors affiliations, country scientific collaborations, institution collaboration networks, keyword analysis, comprehensive of co-occurrence network, thematic map analysis, and 2021 sub-analysis of trend topics was performed. RESULTS: A total of 5623 articles and 16,833 authors from 908 different sources have been identified. The first available document was published in March 2012, while the most recent included was released on the 31st of December 2021. China and USA were the most productive countries. Co-occurrence network analysis identified five words clusters based on top 50 authors' keywords: Radiomics, computed tomography, radiogenomics, deep learning, tomography. Trend topics analysis for 2021 showed an increased interest in artificial intelligence (n = 286), nomogram (n = 166), hepatocellular carcinoma (n = 125), COVID-19 (n = 63), and X-ray computed (n = 60). CONCLUSIONS: Our work demonstrates the importance of bibliometrics in aggregating information that otherwise would not be available in a granular analysis, detecting unknown patterns in Radiomics publications, while highlighting potential developments to ensure knowledge dissemination in the field and its future real-life applications in the clinical practice. CLINICAL RELEVANCE STATEMENT: This work aims to shed light on the state of the art in radiomics, which offers numerous tangible and intangible benefits, and to encourage its integration in the contemporary clinical practice for more precise imaging analysis. KEY POINTS: • ML-based bibliometric analysis is fundamental to detect unknown pattern of data in Radiomics publications. • A raising interest in the field, the most relevant collaborations, keywords co-occurrence network, and trending topics have been investigated. • Some pitfalls still exist, including the scarce standardization and the relative lack of homogeneity across studies.

Comparison of automated segmentation techniques for magnetic resonance images of the prostate.

BACKGROUND: Contouring of anatomical regions is a crucial step in the medical workflow and is both time-consuming and prone to intra- and inter-observer variability. This study compares different strategies for automatic segmentation of the prostate in T2-weighted MRIs. METHODS: This study included 100 patients diagnosed with prostate adenocarcinoma who had undergone multi-parametric MRI and prostatectomy. From the T2-weighted MR images, ground truth segmentation masks were established by consensus from two expert radiologists. The prostate was then automatically contoured with six different methods: (1) a multi-atlas algorithm, (2) a proprietary algorithm in the Syngo.Via medical imaging software, and four deep learning models: (3) a V-net trained from scratch, (4) a pre-trained 2D U-net, (5) a GAN extension of the 2D U-net, and (6) a segmentation-adapted EfficientDet architecture. The resulting segmentations were compared and scored against the ground truth masks with one 70/30 and one 50/50 train/test data split. We also analyzed the association between segmentation performance and clinical variables. RESULTS: The best performing method was the adapted EfficientDet (model 6), achieving a mean Dice coefficient of 0.914, a mean absolute volume difference of 5.9%, a mean surface distance (MSD) of 1.93 pixels, and a mean 95th percentile Hausdorff distance of 3.77 pixels. The deep learning models were less prone to serious errors (0.854 minimum Dice and 4.02 maximum MSD), and no significant relationship was found between segmentation performance and clinical variables. CONCLUSIONS: Deep learning-based segmentation techniques can consistently achieve Dice coefficients of 0.9 or above with as few as 50 training patients, regardless of architectural archetype. The atlas-based and Syngo.via methods found in commercial clinical software performed significantly worse (0.855[Formula: see text]0.887 Dice).

The T-N tract involvement as a new prognostic factor for PORT in locally advanced oral cavity tumors.

OBJECTIVE: The space comprised between tumor and neck lymph nodes (T-N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T-N tract involvement on the postoperative radiotherapy (PORT) outcomes. MATERIALS AND METHODS: Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow-up of six months. RESULTS: One hundred and fifty-seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T-N tract involvement had no impact on both OS (p = .09) and LRFS (p = .2). Among the non-PORT cohort, both OS (p = .007) and LRFS (p = .017) were worse for pts with positive T-N tract compared to those with negative T-N tract. PORT improved both OS (p = .008) and LRFS (p = .003) in pts with positive T-N tract but not in those with negative T-N tract (p = .36 and p = .37, respectively). CONCLUSIONS: Our results suggest that involvement of T-N tract should be considered as prognostic factors informing the indication to PORT.

Reirradiation of head and neck squamous cell carcinomas: a pragmatic approach, part II: radiation technique and fractionations.

INTRODUCTION: Reirradiation (reRT) of local recurrent/second primary tumors of the head and neck represents a potential curative treatment for patients not candidate to a salvage surgery. Aim of the present study is to summarize literature data on modern radiation techniques and fractionations used in this setting of patients. MATERIALS AND METHODS: A narrative review of the literature was conducted on three topics: (1) target volume delineation (2) reRT dose and techniques and (3) ongoing studies. Patients treated with postoperative reRT and palliative intent were not considered for the current analysis. RESULTS: Recommendations on the target volume contouring have been reported. 3D-Conformal Radiotherapy, Intensity Modulated Radiotherapy, Stereotactic body Radiotherapy Intraoperative Radiotherapy, Brachytherapy and Charged Particles have been analyzed in terms of indication and fractionation in the field of reRT. Ongoing studies on the topic have been reported for IMRT and Charged Particles. Moreover, according to literature data a stepwise approach has been proposed aiming to provide a useful tool to select patients candidate to a curative reRT in daily clinical practice. Two clinical cases were also provided for its application. CONCLUSION: Different radiation techniques and fractionations can be used for a second course of radiotherapy in patients with recurrent/second primary tumor of head and neck region. Tumor characteristics as well as radiobiological considerations should be take into account to define the best reRT approach.

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature.

PURPOSE: To critically review available literature on hypofractionated (≥ 3 Gy/fraction) proton therapy (PT) for breast cancer (BCa). METHODS: A systematic screening of the literature was performed in April 2021 in compliance with the preferred reporting items for systematic reviews and meta-analyses recommendations. All full-text publication written in English were considered eligible. Acute and late toxicities, oncological outcomes and dosimetric features were considered for the analysis. RESULTS: Twelve publications met the inclusion criteria; all studies but one focused on accelerated partial breast irradiation (APBI). Eleven works considered post-operative patients, one referred to ABPI as a curative-intent modality. The dosimetric profile of PT compared favorably with both photon-based 3D conformal and intensity-modulated techniques, while a more extended follow-up is warranted to fully assess both the long-term toxicities and the non-inferiority of oncological outcomes. CONCLUSION: Our work shows that results on PT for BCa are currently only available for APBI applications, with dosimetric analyses demonstrating a clear advantage over both 3D conformal and intensity modulated X-rays techniques, especially when ≥ 2 treatment fields were used. However, further evidence is needed to define whether such theoretical benefit translates into clinical improvements, especially in the long-term.

Correlation between radiological and biological features and clinical outcomes in early prostate cancer: an exploratory subgroup analysis.

PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (PCa). In the same manner, multiparametric magnetic resonance imaging (mp-MRI) guided core biopsy is a powerful tool for PCa detection and staging. The aim of the study is to assess whether a correlation can be identified between the pathological stage defined by an mp-MRI-guided core biopsy and Ki-67 expression and PTEN deletion. Such correlation might be useful for staging and treatment personalization in PCa. This investigation was conducted in the context of phase II clinical study "Short-term radiotherapy for early prostate cancer with a concomitant boost to the dominant lesion" (AIRC IG-13218), ClinicalTrials.gov identifier: NCT01913717. Nineteen patients underwent a further in-bore MRI-targeted core biopsy (MRI-TBx) on the dominant intraprostatic lesion (DIL); on this basis, an additional Gleason Score (GS) was determined. PTEN loss and Ki-67 expression on these samples were analyzed and correlated with both risk categories modifications and oncological outcomes (overall survival, biochemical and clinical relapse). GS was upgraded in 5 cases, with 4 patients re-classified as intermediate-risk and 1 patient as high-risk. The latter experienced a clinical local relapse. No correlations between up/down-staging, PTEN deletion, and Ki-67 expression were observed in this cohort. Further investigations are needed towards the identification of a pattern in the tumor aggressiveness-response in PCa treated with ultra-hypofractionated radiotherapy. Moreover, a possible relationship between biomarker analysis and imaging textural features could be explored.

Postsurgical geometrical variations of tumor bed and brainstem during photon and proton therapy for pediatric tumors of the posterior fossa: dosimetric impact and predictive factors.

PURPOSE: Brainstem radionecrosis is an important issue during the irradiation of tumors of the posterior fossa. The aim of the present study is to analyze postsurgical geometrical variations of tumor bed (TB) and brainstem (BS) and their impact on dosimetry. METHODS: Retrospective collection of data from pediatric patients treated at a single institution. Availability of presurgical magnetic resonance imaging (MRI) was verified; availability of at least two postsurgical MRIs was considered a further inclusion criterion. The following metrics were analyzed: total volume, Dice similarity coefficient (DSC), and Haudsdorff distances (HD). RESULTS: Fourteen patients were available for the quantification of major postsurgical geometrical variations of TB. DSC, HD max, and HD average values were 0.47 (range: 0.08;0.76), 11.3 mm (7.7;24.5), and 2.6 mm (0.7;6.7) between the first and the second postoperative MRI, respectively. Postsurgical geometrical variations of the BS were also observed. Coverage to the TB was reduced in one patient (D95: -2.9 Gy), while D2 to the BS was increased for the majority of patients. Overall, predictive factors for significant geometrical changes were presurgical gross tumor volume (GTV) > 33 mL, hydrocephaly at diagnosis, Luschka foramen involvement, and younger age (≤ 8 years). CONCLUSION: Major volume changes were observed in this cohort, with some dosimetric impact. The use of a recent co-registration MRI is advised. The 2-3 mm HD average observed should be considered in the planning target volume/planning organ at risk volume (PTV/PRV) margin and/or robust optimization planning. Results from wider efforts are needed to verify our findings.

MRI-based radiomics signature for localized prostate cancer: a new clinical tool for cancer aggressiveness prediction? Sub-study of prospective phase II trial on ultra-hypofractionated radiotherapy (AIRC IG-13218).

OBJECTIVES: Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa). METHODS: This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis. RESULTS: Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94. CONCLUSIONS: MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice. KEY POINTS: • A radiomic model was used to classify PCa aggressiveness. • Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland. • The most predictive features belong to the texture (57%) and intensity (43%) domains.

Correction to: Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

Unfortunately, the denomination of the IEO was incorrectly published in the affiliation of this original.

Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

PURPOSE: To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT). METHODS AND MATERIALS: We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS. CONCLUSIONS: A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy.

BACKGROUND: There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. METHODS: This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. RESULTS: Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. CONCLUSIONS: Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

Nutritional Intervention for Nonsurgical Head and Neck Cancer Patients Treated with Radiation Therapy: Results from a Prospective Stepped-Wedge Clinical Protocol.

AIM: To evaluate the impact on weight loss (WL) of a standardized nutritional stepped-wedge protocol on consecutive head and neck cancer (HNC) patients treated with curative radiotherapy (RT). METHODS: We prospectively collected data of patients followed by a trained dietitian and treated according to a pre-defined stepped-wedge protocol. Patients with swallowing defect at the baseline and WL >10% 3 months prior to the beginning of RT were excluded from the analysis. Nutritional status was assessed at the baseline and weekly during the course of RT. Fluid and caloric intake were assessed through a 24-h recall. RESULTS: Between May 2010 and March 2011, 42 patients treated were evaluated. Median overall treatment time was 52.5 days. WL per CTCAE 4.03 was G0, G1 and G2 in 23 (55%), 14 (33%) and 5 (12%) patients, respectively. Thirty-five (83%) patients did not require enteral nutrition. About 90% of patients completed RT without interruption of oral feeding. CONCLUSIONS: Despite the high toxicity profile of curative RT in HN, we proposed a standardized stepped-wedge protocol allowing to prevent severe WL in most of our patients. Further larger prospective studies are warranted to validate our approach and to achieve consensus on nutritional intervention in this subset of patients.

Microbiome dynamics, antibiotic resistance gene patterns and spoilage-associated genomic potential in fresh anchovies stored in different conditions.

Fresh fish is a highly perishable product and is easily spoiled by microbiological activity and chemical oxidation of lipids. However, microbial spoilage is the main factor linked with the rapid fish sensorial degradation due to the action of specific spoilage organisms (SSOs) that have the ability to dominate over other microorganisms and produce metabolites responsible for off-flavours. We explored the microbial dynamics in fresh anchovies stored in different packaging (air, modified atmosphere, under vacuum) and temperatures (0, 4 and 10 °C) using shotgun metagenomics, highlighting the selection of different microbial species according to the packaging type. Indeed, Pseudoalteromonas nigrifaciens, Psychrobacter cryohalolentis and Ps. immobilis, Pseudomonas deceptionensis and Vibrio splendidus have been identified as the main SSOs in aerobically stored anchovies, while Shewanella baltica, Photobacterium iliopiscarium, Ps. cryohalolentis and Ps. immobilis prevailed in VP and MAP. In addition, we identified the presence of spoilage-associated genes, leading to the potential production of biogenic amines and different off-flavors (H2S, TMA). In particular, the abundance of microbial genes leading to BA biosynthesis increased at higher storage temperature, while those related to H2S and TMA production were enriched in aerobically and VP packed anchovies, suggesting that MAP could be an effective strategy in delaying the production of these compounds. Finally, we provided evidence of the presence of a wide range of antibiotic resistance genes conferring resistance to different classes of antibiotic (ß-lactams, tetracyclines, polymyxins, trimethoprims and phenicols) and highlighted that storage at higher temperature (4 and 10 °C) boosted the abundance of ARG-carrying taxa, especially in aerobically and MAP packed fish.

Microbiome mapping in beef processing reveals safety-relevant variations in microbial diversity and genomic features.

The microbiome of surfaces along the beef processing chain represents a critical nexus where microbial ecosystems play a pivotal role in meat quality and safety of end products. This study offers a comprehensive analysis of the microbiome along beef processing using whole metagenomics with a particular focus on antimicrobial resistance and virulence-associated genes distribution. Our findings highlighted that microbial communities change dynamically in the different steps along beef processing chain, influenced by the specific conditions of each micro-environment. Brochothrix thermosphacta, Carnobacterium maltaromaticum, Pseudomonas fragi, Psychrobacter cryohalolentis and Psychrobacter immobilis were identified as the key species that characterize beef processing environments. Carcass samples and slaughterhouse surfaces exhibited a high abundance of antibiotic resistance genes (ARGs), mainly belonging to aminoglycosides, ß-lactams, amphenicols, sulfonamides and tetracyclines antibiotic classes, also localized on mobile elements, suggesting the possibility to be transmitted to human pathogens. We also evaluated how the initial microbial contamination of raw beef changes in response to storage conditions, showing different species prevailing according to the type of packaging employed. We identified several genes leading to the production of spoilage-associated compounds, and highlighted the different genomic potential selected by the storage conditions. Our results suggested that surfaces in beef processing environments represent a hotspot for beef contamination and evidenced that mapping the resident microbiome in these environments may help in reducing meat microbial contamination, increasing shelf-life, and finally contributing to food waste restraint.

Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report.

PURPOSE: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. METHODS: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. RESULTS: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. CONCLUSIONS: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.

3D-printed boluses for radiotherapy: influence of geometrical and printing parameters on dosimetric characterization and air gap evaluation.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry.