Search

BackgroundDigital health technologies offer the potential to improve the daily lives of older adults, maintain their health efficiently, and allow aging in place. Despite increasing evidence of benefits and advantages, readiness for adopting digital interventions among older people remains underexplored. ObjectiveThis study aims to explore the relationships between sociodemographic-, health-, and lifestyle-related factors and technology use in everyday life and community-dwelling older adults’ readiness to adopt telemedicine, smartphones with texting apps, wearables, and robotics. MethodsThis was a cross-sectional, population-based survey study with a stratified probabilistic sample of adults aged 75 years or older living in South Tyrol (autonomous province of Bolzano/Bozen, Italy). A random sample of 3600 community-dwelling older adults living at home was invited to complete a questionnaire including single items (older adults’ readiness to use health technology) and scales (PRISMA-7; Program of Research on Integration of Services for the Maintenance of Autonomy). Descriptive and logistic regression analyses were performed to analyze the data. ResultsIn total, 1695 community-dwelling older adults completed the survey (for a response rate of 47%). In terms of potential digital health technology adoption, wearable devices were favored by 33.7% (n=571), telemedicine by 30.1% (n=510), smartphones and texting apps by 24.5% (n=416), and assistant robots by 13.7% (n=232). Sociodemographic-, health- and lifestyle-related factors, as well as the use of technology in everyday life, played a significant role in explaining readiness to adopt digital health technologies. For telemedicine, age ≥85 years (odds ratio [OR] 0.74, 95% CI 0.56-0.96), financial constraints (OR 0.68, 95% CI 0.49-0.95), and less than 2 hours of physical activity per week (OR 0.75, 95% CI 0.58-0.98) were associated with nonreadiness, while Italian-speaking participants (OR 1.54, 95% CI 1.16-2.05) and those regularly using computers (OR 1.74, 95% CI 1.16-2.60), smartphones (OR 1.69, 95% CI 1.22-2.35), and the internet (OR 2.26, 95% CI 1.47-3.49) reported readiness for adoption. ConclusionsCommunity-dwelling older adults display varied readiness toward the adoption of digital health technologies, influenced by age, mother tongue, living situation, financial resources, physical activity, and current use of technology. The findings underscore the need for tailored interventions and educational programs to boost digital health technology adoption among community-dwelling older adults.

Background Withdrawal of reimbursement for low-value care through a policy change, ie, active disinvestment, is considered a potentially effective de-implementation strategy. However, previous studies have shown conflicting results and the mechanism through which active disinvestment may be effective is unclear. This study explored how the active disinvestment initiative regarding subacromial decompression (SAD) surgery for subacromial pain syndrome (SAPS) in the Netherlands influenced clinical decision-making around surgery, including the perspectives of orthopedic surgeonsand hospital sales managers.Methods We performed 20 semi-structured interviews from November 2020 to October 2021 with ten hospital sales managers and ten orthopedic surgeons from twelve hospitals across the Netherlands as relevant stakeholders in the active disinvestment process. The interviews were video-recorded and transcribed verbatim. Inductive thematic analysis was used to analyse interview transcripts independently by two authors and discrepancies were resolved through discussion.Results Two overarching themes were identified that negatively influenced the effect of the active disinvestment initiative for SAPS. The first theme was that the active disinvestment represented a “Too small piece of the pie” indicating little financial consequences for the hospital as it was merely used in negotiations with healthcare insurers to reduce costs, required a disproportionate amount of effort from hospital staff given the small saving-potential, and was not clearly defined nor enforced in the overall healthcare insurer agreements. The second theme was “They [healthcare insurer] got it wrong,” as the evidence and guidelines had been incorrectly interpreted, the active disinvestment was at odds with clinician experiences and beliefs and was perceived as a reduction in their professional autonomy.Conclusion The two overarching themes and their underlying factors highlight the complexity for active disinvestment initiatives to be effective. Future de-implementation initiatives including active disinvestment should engage relevant stakeholders at an early stage to incorporate their different perspectives, gain support and increase the probability of success.

Altruism plays an essential role in promoting vaccine uptake, an issue that came to the fore during the COVID-19 pandemic through discussions of herd immunity and altruistic motivations. In response, the primary objective of this cross-sectional survey was to explore how altruistic attitudes have evolved in the post-pandemic era and to assess their effectiveness in motivating vaccination behavior in different age groups. The study aimed to elucidate changes in altruistic motivations for vaccination and their implications for public health strategies. Using a representative sample of the adult population of South Tyrol, Italy, including 1388 participants, altruism was assessed in 2023 with the scales of the Elderly Care Research Center (ECRC) and the International Personality Item Pool (IPIP) subscale of the version 5F30F-R1. Its association with demographic variables, vaccination attitudes and personal beliefs in two age groups (18–69 years, 70+ years) was analyzed. The results reveal distinct predictors of altruism across these scales and age groups, suggesting a shift in altruistic attitudes towards vaccination when comparing data from a similar survey conducted in 2021 with the 2023 results. Consequently, the use of altruism scales for different age groups is warranted. This study highlights the need for further research in this field. It concludes that while promoting altruistic behavior to increase vaccine uptake appears to be effective primarily among the younger population, emphasizing personal safety is more appropriate for encouraging vaccination among older individuals.

This study examines vaccine agreements in South Tyrol, Italy, within distinct socio-cultural and linguistic contexts. Using data from the 2021 and 2023 “COVID-19 Snapshot Monitoring” extended surveys, we assessed changes in attitudes towards COVID-19 and other vaccinations during the second and final years of the pandemic. Multivariate logistic regression analysis was used to examine factors such as trust in institutions, language groups, and the use of complementary and alternative medicine. The representativeness of the study is supported by good participation rates, ensuring a comprehensive view of attitudes towards vaccination in the region. The results show a shift in public agreement with the national vaccination plan to 64% by 2023, from a rate of about 73% agreement in 2021 (p < 0.001). A significant decrease in trust in health authorities and a negative correlation with complementary and alternative medicine consultations were observed. The results highlight the complex nature of vaccine hesitancy in diverse regions such as South Tyrol and underline the need for targeted communication strategies and trust-building initiatives to effectively reduce hesitancy. This study provides critical insights for the formulation of public health strategies in diverse sociocultural settings.

ObjectivesWe aimed to (1) describe the course of the emotional burden (i.e., depression, anxiety, and stress) in a general population sample during the coronavirus pandemic in 2020 and 2021 and (2) explore the association between emotional burden and a serologically proven infection with SARS-CoV-2.Study designThis longitudinal study involved a sample of community-dwelling persons aged ≥14 years from the general population of South Tyrol (Province of Bolzano-Bozen, Northern Italy). Data were collected at two stages over a 1-year period in 2020 and 2021.MethodsPersons were invited to participate in a survey on socio-demographic, health-related and psychosocial variables (e.g., age, chronic diseases, Depression Anxiety Stress Scale, DASS-21), as well as in the serological testing for of SARS-CoV-2-specific immunoglobulins.ResultsIn 2020, 855 (23.8%) out of 3,600 persons participated; in 2021, 305 (35.7%) out of 855 were tested again. We observed a statistically significant decrease in mean DASS-21 scores for depression, stress, and total scores between 2020 and 2021, yet not for anxiety. Persons with a confirmed SARS-CoV-2-infection between the first and second data collection exhibited increased emotional burden compared to those without SARS-CoV-2-infection. The odds of participants with a self-reported diagnosis of mental disorder for future infection with SARS-CoV-2 was almost four times higher than that of participants without mental disorders (OR:3.75; 95%CI:1.79-7.83).ConclusionOur findings support to the hypothesis of a psycho-neuroendocrine-immune interplay in COVID-19. Further research is necessary to explore the mechanisms underlying the interplay between mental health and SARS-CoV-2 infections.

Background and Purpose. The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy. Methods. We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18F-FDG PET/CT before treatment. 18F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c-index was employed to score the predictive power of the multivariate cox regression models. Results. Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P=0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c-index of 0.76 against 0.65 of the model based on clinical variables alone. Conclusion. LILRE, evaluated on pretreatment 18F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control. [ABSTRACT FROM AUTHOR]

Background: During the coronavirus pandemic, altruism has been linked to personal protective behavior, vaccine development, and vaccination intention. Studies of the moderating effects of age on altruism in pandemic preparedness have not yet been conducted. Methods: A representative cross-sectional survey of residents of South Tyrol, Italy, was conducted in March 2021. Among the participants, 1169 were aged 18–69 years, and 257 were aged ≥ 70 years. The questionnaire collected information on sociodemographic and individual characteristics, including comorbidities, COVID-19-related experiences, trust in information, the likelihood of accepting the national vaccination plan, and altruism. A linear regression analysis was performed. Results: Among 1426 participants, the median altruism sum score was 24 (interquartile range, 20–26). In the participant group aged ≥ 70 years, the median altruism score was significantly higher than that in the younger group. Participants living in a single household were significantly less altruistic than other participants, while participants working in the health sector, living in a household at risk from coronavirus disease 2019, or suffering from a chronic disease were found to be more altruistic. Altruism showed significant positive correlations with age and agreement with the national vaccination plan and was negatively correlated with well-being. Trust in institutions was positively correlated with altruism only in the younger age group but not in the elderly. Linear regression models confirmed female gender and identified trust in institutions as a positive predictor of altruism. In the younger age group, increased well-being and restricted individual sports activities were associated with reduced altruism, whereas support of compulsory self-isolation after contact with a SARS-CoV-2-positive person and handwashing as a personal protective measure were positively associated. Conclusion: Altruism is associated with various predictors of pandemic behavior and traits. The strengths of the identified positive and negative correlations support the modifying role of age in the effects of altruism on pandemic attitudes. Interventions that are likely to enhance altruism to improve pandemic preparedness in certain age groups require further study.

Background: The demographic determinants of hesitancy in Coronavirus Disease—2019 (COVID-19) vaccination include rurality, particularly in low- and middle-income countries. In the second year of the pandemic, in South Tyrol, Italy, 15.6 percent of a representative adult sample reported hesitancy. Individual factors responsible for greater vaccination hesitancy in rural areas of central Europe are poorly understood. Methods: A cross-sectional survey on a probability-based sample of South Tyrol residents in March 2021 was analyzed. The questionnaire collected information on sociodemographic characteristics, comorbidities, COVID-19-related experiences, conspiracy thinking, and the likelihood of accepting the national vaccination plan. A logistic regression analysis was performed. Results: Among 1426 survey participants, 17.6% of the rural sample (n = 145/824) reported hesitancy with COVID-19 vaccination versus 12.8% (n = 77/602) in urban residents (p = 0.013). Rural residents were less likely to have post-secondary education, lived more frequently in households with children under six years of age, and their economic situation was worse than before the pandemic. Chronic diseases and deaths due to COVID-19 among close relatives were less frequently reported, and trust in pandemic management by national public health institutions was lower, as was trust in local authorities, civil protection, and local health services. Logistic regression models confirmed the most well-known predictors of hesitancy in both urban and rural populations; overall, residency was not an independent predictor. Conclusion: Several predictors of COVID-19 vaccine hesitancy were more prevalent in rural areas than in urban areas, which may explain the lower vaccine uptake in rural areas. Rurality is not a determinant of vaccine hesitancy in the economically well-developed North of Italy.

Acetaminophen (APAP) is a mild analgesic and antipyretic used commonly worldwide. Although considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), to proteins. The aim of this study was to identify APAP-protein targets in both rat and mouse liver, and to compare the results from both species, using bottom-up proteomics with data-dependent high resolution mass spectrometry and targeted multiple reaction monitoring (MRM) experiments. Livers from rats and mice, treated with APAP, were homogenized and digested by trypsin. Digests were then fractionated by mixed-mode solid-phase extraction prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Targeted LC-MRM assays were optimized based on high-resolution MS/MS data from information-dependent acquisition (IDA) using control liver homogenates treated with a custom alkylating reagent yielding an isomeric modification to APAP on cysteine residues, to build a modified peptide database. A list of putative in vivo targets of APAP were screened from data-dependent high-resolution MS/MS analyses of liver digests, previous in vitro studies, as well as selected proteins from the target protein database (TPDB), an online resource compiling previous reports of APAP targets. Multiple protein targets in each species were found, while confirming modification sites. Several proteins were modified in both species, including ATP-citrate synthase, betaine-homocysteine S-methyltransferase 1, cytochrome P450 2C6/29, mitochondrial glutamine amidotransferase-like protein/ES1 protein homolog, glutamine synthetase, microsomal glutathione S-transferase 1, mitochondrial-processing peptidase, methanethiol oxidase, protein/nucleic acid deglycase DJ-1, triosephosphate isomerase and thioredoxin. The targeted method afforded better reproducibility for analysing these low-abundant modified peptides in highly complex samples compared to traditional data-dependent experiments.

Background: German is a minority language in Italy and is spoken by the majority of the inhabitants of the Autonomous Province of Bolzano, South Tyrol. Linguistic group membership in South Tyrol is an established determinant of health information-seeking behavior. Because the COVID-19 incidence and vaccination coverage in the second year of the pandemic in Italy was the worst in South Tyrol, we investigated whether linguistic group membership is related to COVID-19 vaccine hesitancy. Methods: A cross-sectional survey was conducted on a probability-based sample of 1425 citizens from South Tyrol in March 2021. The questionnaire collected information on socio-demographics, including linguistic group membership, comorbidities, COVID-19-related experiences, conspiracy thinking, well-being, altruism, and likelihood of accepting the national vaccination plan. Multiple logistic regression analyses were performed to identify the significant predictors of vaccine hesitancy. Results: Overall, 15.6 percent of the sample reported vaccine hesitancy, which was significantly higher among German speakers than among other linguistic groups. Increased hesitancy was mostly observed in young age, the absence of chronic disease, rural residence, a worsened economic situation, mistrust in institutions, and conspiracy thinking. In the multiple logistic regression analyses, linguistic group membership was not an independent predictor of vaccine hesitancy. Conclusion: Although German is a minority language in Italy and COVID-19 vaccine hesitancy was higher in the German native language group than in the Italian, linguistic group membership was not an independent predictor of hesitancy in the autonomous province. Known predictors of vaccine hesitancy are distributed unevenly across language groups. Whether language group-specific intervention strategies to promote vaccine hesitancy are useful requires further study.

Polymers crosslinked via furan/maleimide thermo-reversible chemistry have been extensively explored as reprocessable and self-healing thermosets and elastomers. For such applications, it is important that the thermo-reversible features are reproducible after many reprocessing and healing cycles. Therefore, side reactions are undesirable. However, we have noticed irreversible changes in the mechanical properties of such materials when exposing them to temperatures around 150 °C. In this work, we study whether these changes are due to the self-reaction of maleimide moieties that may take place at this rather low temperature. In order to do so, we prepared a furan-grafted polyketone crosslinked with the commonly used aromatic bismaleimide (1,1′-(methylenedi-4,1-phenylene)bismaleimide), and exposed it to isothermal treatments at 150 °C. The changes in the chemistry and thermo-mechanical properties were mainly studied by infrared spectroscopy, 1H-NMR, and rheology. Our results indicate that maleimide self-reaction does take place in the studied polymer system. This finding comes along with limitations over the reprocessing and self-healing procedures for furan/maleimide-based reversibly crosslinked polymers that present their softening (decrosslinking) point at relatively high temperatures. On the other hand, the side reaction can also be used to tune the properties of such polymer products via in situ thermal treatments.

Acetaminophen (APAP)-induced hepatotoxicity is the most common cause of acute liver failure in the Western world. APAP is bioactivated to N-acetyl p-benzoquinone imine (NAPQI), a reactive metabolite, which can subsequently covalently bind to glutathione and protein thiols. In this study, we have used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to characterize NAPQI binding to human glutathione S-transferases (GSTs) in vitro. GSTs play a crucial role in the detoxification of reactive metabolites and therefore are interesting target proteins to study in the context of APAP covalent binding. Recombinantly-expressed and purified GSTs were used to assess NAPQI binding in vitro. APAP biotransformation to NAPQI was achieved using rat liver microsomes or human cytochrome P450 Supersomes in the presence of GSTA1, M1, M2, or P1. Resulting adducts were analyzed using bottom-up proteomics, with or without LC fractionation prior to LC-MS/MS analysis on a quadrupole-time-of-flight instrument with data-dependent acquisition (DDA). Targeted methods using multiple reaction monitoring (MRM) on a triple quadrupole platform were also developed by quantitatively labeling all available cysteine residues with a labeling reagent yielding isomerically-modified peptides following enzymatic digestion. Seven modified cysteine sites were confirmed, including Cys112 in GSTA1, Cys78 in GSTM1, Cys115 and 174 in GSTM2, as well as Cys15, 48, and 170 in GSTP1. Most modified peptides could be detected using both untargeted (DDA) and targeted (MRM) approaches, however the latter yielded better detection sensitivity with higher signal-to-noise and two sites were uniquely found by MRM.

The structure of a continuous-grid chiral cubic phase made of achiral constituent molecules is a hot topic in the field of thermotropic liquid crystals. Several structural models have been proposed so far. Resonant X-ray scattering (RXS), which gives information on the molecular orientation in the unit cell, could be applied to select the most appropriate model. We modeled the RXS response for the recently proposed chiral cubic phase structure with an all-hexagon chiral continuous grid. A tensor form factor of a unit cell is constructed, which enables calculation of intensities of peaks for all Miller indices. We find that all the symmetry allowed peaks are resonantly enhanced, and their intensity is much stronger than the intensity of the symmetry forbidden (resonant) peaks. In particular, we predict that a strong resonant enhancement of the symmetry allowed peaks (011) and (002), not observed in a nonresonant scattering, could be observed by RXS at the carbon absorption edge. By RXS at the sulfur absorption edge, one might observe a resonant peak (113) and resonantly enhanced peak (233), and resonant enhancement of all the peaks that are observed in a nonresonant scattering, which probably hide the rest of the predicted resonant peaks.

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [ 18 F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [ 68 Ga]Ga-PSMA-11 versus [ 18 F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13−38.00 vs. 40.93 months, 95% CI: 40.93−40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

Background: Agreement between planners and treating radiation oncologists (ROs) on plan quality criteria is essential for consistent planning. Differences between ROs and planning medical physicists (MPs) in perceived quality of head and neck cancer plans were assessed., Materials and Methods: Five ROs and four MPs scored 65 plans for in total 15 patients. For each patient, the clinical (CLIN) plan and two or four alternative plans, generated with automated multi-criteria optimization (MCO), were included. There was always one MCO plan aiming at maximally adhering to clinical plan requirements, while the other MCO plans had a lower aimed quality. Scores were given as follows: 1-7 and 1-2, not acceptable; 3-5, acceptable if further planning would not resolve perceived weaknesses; and 6-7, straightway acceptable. One MP and one RO repeated plan scoring for intra-observer variation assessment., Results: For the 36 unique observer pairs, the median percentage of plans for which the two observers agreed on a plan score (100% = 65 plans) was 27.7% [6.2, 40.0]. In the repeat scoring, agreements between first and second scoring were 52.3% and 40.0%, respectively. With a binary division between unacceptable (scores 1 and 2) and acceptable (3-7) plans, the median inter-observer agreement percentage was 78.5% [63.1, 86.2], while intra-observer agreements were 96.9% and 86.2%. There were no differences in observed agreements between RO-RO, MP-MP, and RO-MP pairs. Agreements for the highest-quality, automatically generated MCO plans were higher than for the CLIN plans., Conclusions: Inter-observer differences in plan quality scores were substantial and could result in inconsistencies in generated treatment plans. Agreements among ROs were not better than between ROs and MPs, despite large differences in training and clinical role. High-quality automatically generated plans showed the best score agreements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cagni, Botti, Rossi, Iotti, Iori, Cozzi, Galaverni, Rosca, Sghedoni, Timon, Spezi and Heijmen.)

Background and Purpose: The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18 F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy., Methods: We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18 F-FDG PET/CT before treatment. 18 F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c -index was employed to score the predictive power of the multivariate cox regression models., Results: Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P =0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c -index of 0.76 against 0.65 of the model based on clinical variables alone., Conclusion: LILRE, evaluated on pretreatment 18 F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control.

Aim: To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment., Material and Methods: Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy., Results: Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02)., Conclusions: Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

Aim: Intraoperative radiotherapy (IORT) has been investigated as an exclusive adjuvant treatment option for early-stage breast cancer (BC). We analysed our experience on the technical aspects of this innovative approach in terms of identification of breast volume actually to be treated during IORT., Patients and Methods: A total of 315 patients at low risk of breast cancer recurrence underwent IORT as exclusive treatment after breast-conservative surgery. To evaluate the breast volume actually irradiated with IORT, we considered a sample of eight patients, chosen retrospectively as having enough clips to identify the tumour bed and IORT site in computed-tomography (CT). The clinical target volume (CTV) was assessed for each patient with two different methods: the first, cc-IORT, was considered during surgery according to the chosen collimator diameter and glandular thickness, while the second, cc-CT, was evaluated through computed-tomography performed after surgery. The cc-CT CTV was obtained by contouring the cc-IORT on the CT section on the basis of the clips placed by the surgeon on the resection margins., Results: In our experience, the 5-cm (50%) and the 6-cm (36%) diameter collimators have been the ones, used the most. The diameter of the collimator used did not appear to adversely affect the satisfactory aesthetic result. The comparison between CTVs showed that glandular breast volume contoured with CT (cc-CT) appeared to be three fold larger than the target identified at surgery and included in the area of chosen collimator (cc-IORT)., Conclusion: The actual volume of breast gland irradiated with the IORT procedure appears to be larger than expected. This may be due to the area being prepared for IORT by placing tissue compactly.

Aim: To assess the impact of a two-step multiparameter selection on the actual enrollment of women with breast cancer into a prospective intraoperative radiotherapy (IORT) trial., Patients and Methods: From September 2009, a prospective clinical trial was started in order to deliver adjuvant exclusive single -fraction IORT to patients with early breast cancer. To select patients meeting suitable eligibility criteria for the clinical trial, a two-step decision process was developed: at pre-surgical examination (first step) and during surgery (second step)., Results: A series of 464 patients with breast cancer was analysed: at the first step, out of 464 patients, 333 (71%) were considered eligible for the IORT protocol; at the second step, out of 333 patients, 199 (60%) met the eligibility criteria and received the IORT fraction according to the criteria of the controlled trial., Conclusion: In our experience, the ultimate rate of patients who enrolled in the IORT clinical trial after the two-step decision process was 43%.