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Nel contesto di una società in continua e rapida evoluzione, la morte si ripresenta come una ineludibile tematica di peculiare urgenza esistenziale. Sebbene, infatti, il progresso tecnologico e delle scienze mediche abbia facilitato una risposta tecnica alla domanda di salute che sempre di più incontra metodiche multimodali e multidisciplinari di terapia, la tecnologia di cura relega spesso il paziente ad una solitudine esistenziale dove, pur in presenza di una terapia per la sua malattia, non trova spazio una relazione di cura per la sua sofferenza. Questa dicotomia della cura, che si suddivide da una parte nel “trattare” dall’altra nell’“essere presente”, porta, soprattutto nel contesto del fine vita, al rischio di attestare la cura al solo livello tecnico, rendendo ‘giustificata’ la richiesta del paziente al medico di ‘somministrare il fine vita’, sopprimendo l’eco relazionale di ritorno del medico di fronte al bisogno umano del paziente. Lo scopo di questo articolo è di recuperare le riflessioni legate all’esperienza clinica ed umana propedeutiche ad accompagnare il paziente in un percorso relazionale offrendogli, nelle varie fasi della cura, una “eco di ritorno”, utili a non comprimere la percezione del medico a livello di somministratore automatico.

Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT.The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected.One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities.In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown.To assess the effectiveness of VDZ in this setting.All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up.Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%).VDZ may be an effective option for the treatment of postoperative recurrence of CD.

Background Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids. Methods This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction–confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes. Results Data on 122 patients (mean age, 43.9 ± 16.7 years; males, 50.0%; Crohn’s disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006–1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104–164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320–178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076). Conclusions In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19.

Uveal melanoma (UM) is the most common intra-ocular tumor in Caucasian adults and may derive from melanocytes. Historically, the first therapeutic approach to treat UM has been surgical removal of the eye, with obvious consequences in terms of function, cosmesis, and psychological impact on patients. Collaborative Ocular Melanoma Study (COMS) introduced the first uniform approach to perform interventional radiotherapy (IRT - brachytherapy) procedure in a standardized way that allowed to demonstrate equivalence of IRT with enucleation in terms of overall survival. Since this milestone, several international guidelines have been issued with regard to several technical aspects of this procedure, which has become the mainstream therapy worldwide. However, nowadays, there is still a lack of consensus about the criteria to definitively assess UM response after IRT. We present a collection of paradigmatic cases treated in our institution, and then discuss in detail the latest available evidence on the topic.

Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as “co-stars” in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization.

There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calculated to find the cutoffs.107 patients were included. Patients who achieved ER had significantly lower baseline NLR (p = 0.025), ELR (p = 0.013), and ENLR (p = 0.020) compared with those without ER; results after 12 weeks of treatment for ELR (p = 0.006) and ENLR (p = 0.003). AUC was 0.64 (p = 0.003), 0.67 (p = 0.006) and 0.65 (p = 0.014) for NLR, ELR and ENLR.Low NLR, ELR and ENLR can predict ER and could be used in clinical practice for a better management of CD patients.

New digital technologies can become a tool for welcoming the patient through the artistic dimension. Cancer patients, in particular, need support that accompanies and supports them throughout their treatment.The Art4ART project consist in the structural proposal to cancer patients of a web-based digital platform containing several forms of art as video-entertainments; a multimedia immersive room; an art-based welcoming of the patients with several original paintings; an environment with a peacefulness vertical garden; a reconceptualization of the chemotherapy-infusion seats. Data regarding patients' preference and choices will be stored and analysed also using artificial intelligence (AI) algorithm to measure and predict impact indicators regarding clinical outcomes (survival and toxicity), psychological indicators. Moreover, the same digital platform will contribute to a better organization of the activities.Through the systematic acquisition of patient preferences and through integration with other clinical parameters, it will be possible to measure the clinical, psychological, organisational, and social impact of the newly implemented Art4ART project. The use of digital technology leads us to apply the reversal of viewpoint from

Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded. Evidence for vedolizumab is controversial, as it was associated both with improvement and development of arthralgias, while ustekinumab, the first anti-interleukin 12/23 (IL-12/23) approved for IBD, has demonstrated good efficacy, especially in peripheral arthritis, and more IL-23 inhibitors are being developed in IBD. Tofacitinib was the first Janus kinase (JAK) inhibitor to be approved in IBD, and as it demonstrated efficacy in treating ankylosing spondylitis, it may represent a good choice in axial arthritis, while more selective JAK inhibitors are yet to be approved. Unexpectedly, the first anti-IL17 that was studied in IBD (secukinumab) has shown not to be effective in treating IBD, and the role of anti-IL17 drugs in these diseases needs further investigation. Therefore, as availability of biologics and small molecules is increasing, their positioning in clinical practice is becoming more and more challenging, and multidisciplinary management needs to be implemented in both research and clinical settings in order to enhance early recognition of SpA in IBD patients, optimize treatment and ultimately improve the patients' quality of life.

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB–IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46–56 years). The median follow-up was 12 months (range 0–60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

Metabolic diseases are rare genetic conditions in the paediatric age. The diagnostic process is often complex and the diagnosis comes even years after the onset of symptoms. The article presents the only documented case of Morquio syndrome and hereditary spherocytosis managed in a second-level Centre using enzyme replacement therapy.

Esophagogastric junction (EGJ) carcinoma represents a specific site of disease, given the opportunities for multimodal clinical care and management and the possibilities of combined treatments. It encompasses various clinical subgroups of disease that are heterogeneous and deserve different treatments; therefore, the guidelines have progressively evolved over time, considering the evidence provided by clinical trials. The aim of this narrative review was to summarize the main evidence, which orientates the current guidelines, and to collect the main ongoing studies to address existing gray areas.

Additional file 1. Confusion matrices of the predictive performances for the intercontinenental cohort.

In the context of the SARS-CoV-2 pandemic, it is important to ensure the quality of cancer treatment as well as patients and health professionals' safety. Individual-based treatment options should be considered in patients with advanced epithelial skin cancer, who are typically elderly and frail. Aim of this study was to assess feasibility and safety of Contact Skin Radiation Therapy (CSRT) to treat basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) during SARS-CoV-2 pandemic. Patients with advanced and difficult-to-treat BCC or SCC were discussed at skin multidisciplinary tumor board (S-MDTB) from February the 21st to May the 4th (phase 1 Italian Pandemic) and retrospectively analyzed. Patient's triage following internal recommendations was daily performed. CSRT was delivered in 8 fractions of 5 Gy each, twice a day. Beyond the clinical outcomes, treatment success indicators, such as the completion of CSRT without SARS-CoV-2 occurrence, were identified to evaluate the feasibility of CSRT during pandemic. A post-treatment psychological assessment regarding patient's safety perception was performed. Six male patients (median age 80 years; range 62-92) with histologically confirmed BCC or SCC were treated with CSRT. Complete clinical remission was achieved in 5/6 patients (83.4%). No high-grade acute toxicities occurred during treatment. No patients or healthcare personnel developed SARS-CoV-2 infection. All the treatment success indicators were achieved. CSRT represents a safe, and feasible treatment option even during the pandemic emergency period. Hypofractionation could be an option to reduce total number of fractions and, consequently, infective risk exposition.

Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy.To define if it is necessary reduce immunosuppression drugs during radiotherapy.The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND" and "OR" Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated.The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type.The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic cancer with poor outcomes in locally advanced disease. This study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of exclusive (chemo)radiotherapy (eRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer radical raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Seven Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 90 patients (patient populations shown in table 1), with a median age of 76 years (range 32-92). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (26%); instead, the rate of severe skin fibrosis was 4.4%. After a median follow-up of 10 months (range 1-199), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 42.2%, 40%, and 36.7%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. Clinical outcomes are still confirmed to be poor. The results suggest the clinical evaluation of the impact of treatment standardisation, in terms of doses and volumes, in a further perspective study.

Introduction/Background* Vulvar cancer (VC) is a rare gynaecologic malignancy. The study aims to evaluate in a retrospective, multicentred, real-world dataset of patients affected by VC efficacy and safety of adjuvant (chemo)radiotherapy (aRT), focusing especially to the treatment prescription among participant centers joining the Observational itaLian stuDy on vuLvar cAncer adjuvant raDiotherapY (OLDLADY) project endorsed by the GYN study group of the AIRO (Italian Association of Radiotherapy and Clinical Oncology). Methodology Patients affected by VC and treated by eRT from January 2010 to December 2018 in Nine Italian radiotherapy centers were retrospectively included and clinical data were collected, analysing tumour staging, treatment prescription, clinical and toxicity outcomes. Result(s)* The multicentred retrospective cohort was composed by 181 patients (patient populations shown in table 1), with a median age of 71.5 years (range 17-90). A considerable heterogeneity was found in the treatment prescription, radiotherapy doses and concomitant chemotherapy schedules. The most relevant acute toxicity revealed for the patient cohort was skin toxicity (22.1%); instead, the rate of severe chronic lymphoedema was 1.1%. After a median follow-up of 30 months (range 1-185), the 2-year actuarial local control rate (LC), the 2-year disease free survival rate (DFS) and the overall survival rate (OS) were 57.2%, 49.4%, and 55.1%, respectively. Kaplan-Meier curves were computed and reported in figure 1. Conclusion* A diverse spectrum of radiotherapy options to exclusively treat patients affected by VC was reported. To achieve higher treatment standardisation, in terms of prescribed doses and volumes, this study suggest further cooperative prospective studies.

Radiotherapy is highly involved in the management of prostate cancer. Its features and potential applications experienced a radical evolution over last decades, as they are associated to the continuous evolution of available technology and current oncological innovations. Some application of radiotherapy like brachytherapy have been recently enriched by innovative features and multidisciplinary dedications. In this report we aim to put some questions regarding the following issues regarding multiple aspects of modern application of radiation oncology: the current application of radiation oncology; the modern role of stereotactic body radiotherapy (SBRT) for both the management of primary lesions and for lymph-nodal recurrence; the management of the oligometastatic presentations; the role of brachytherapy; the aid played by the application of the organ at risk spacer (spacer OAR), fiducial markers, electromagnetic tracking systems and on-line Magnetic Resonance guided radiotherapy (MRgRT), and the role of the new opportunity represented by radiomic analysis.

The Objective Breast Cosmesis Scale (OBCS) is an objective method that documents the aesthetic changes in breast cancer patients. This work evaluates the kOBCS© software (http://www.kobcs.info) which simplifies the estimation of the OBCS values. Five schematic drawings were photographed and imported into the kOBCS©. Thirty photos of breast cancer patients were imported into kOBCS©; 20 users (experts and non-experts) evaluated the photographs on two different settings. Subjective evaluation was performed using the Harvard breast cosmesis scale. There was a highly significant correlation between the OBCS values based on hand measurements and the values estimated by kOBCS© (r = 0.997, P

Background Predicting pathological complete response (pCR) in patients affected by locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (nCRT) is a challenging field of investigation, but many of the published models are burdened by a lack of reliable external validation. Aim of this study was to evaluate the applicability of a magnetic resonance imaging (MRI) radiomic-based pCR model developed and validated in Europe, to a different cohort of patients from an intercontinental cancer center. Methods The original model was based on two clinical and two radiomics features extracted from T2-weighted 1.5 T MRI of 161 LARC patients acquired before nCRT, considered as training set. Such model is here validated using the T2-w 1.5 and 3 T staging MRI of 59 LARC patients with different clinical characteristics consecutively treated in mainland Chinese cancer center from March 2017 to January 2018. Model performance were evaluated in terms of area under the receiver operator characteristics curve (AUC) and relative parameters, such as accuracy, specificity, negative and positive predictive value (NPV and PPV). Results An AUC of 0.83 (CI 95%, 0.71–0.96) was achieved for the intercontinental cohort versus a value of 0.75 (CI 95%, 0.61–0.88) at the external validation step reported in the original experience. Considering the best cut-off threshold identified in the first experience (0.26), the following predictive performance were obtained: 0.65 as accuracy, 0.64 as specificity, 0.70 as sensitivity, 0.91 as NPV and 0.28 as PPV. Conclusions Despite the introduction of significant different factors, the proposed model appeared to be replicable on a real-world data extra-European patients’ cohort, achieving a TRIPOD 4 level.

Background To compare the late toxicity rates after two different high dose rate (HDR) adjuvant intravaginal interventional radiotherapy (IRT-brachytherapy) dose schedules in stage I-II endometrial cancer. Methods Stage I-II patients with endometrial cancer treated with surgery (with or without lymphadenectomy) and adjuvant HDR-IRT between 2014 and 2020 were included in this analysis. Patients were treated with two schedules. In the first cohort (C1), 21 Gy were delivered in three weekly fractions (7 Gy) prescribed 0.5 cm from the applicator surface. In the second cohort (C2), 24 Gy were delivered in four weekly fractions (6 Gy). The clinical target volume was the upper third of the vagina for C1 and the upper 3 cm for C2. HDR-IRT technique and point prescription (5 mm depth from the applicator surface) were the same for all patients. Vaginal toxicity was scored according to the CTCAE 5.0 scale in terms of the presence versus absence of any toxicity grade. The correlation among toxicity and clinical covariates (age, lymphadenectomy, fractionation, stage) was tested by Pearson correlation test (univariate) and by logistic regression (multivariable). Results 114 stage I and three stage II patients, median age 62 (range: 32–85) years, were included in this analysis. The mean follow-up was 56.3 months in C1 (40–76) and 20 months in C2 (8–42). Vaginal late toxicity was recorded in 40 and 15 patients in C1 and 2, respectively. Age, lymphadenectomy, and fractionation were significantly correlated with toxicity at univariate analysis (p value = 0.029, 0.006, and 0.002, respectively), while stepwise logistic regression confirmed only age and fractionation as significantly correlated parameters (p value = 0.02 and 0.001, respectively). Three-year local relapse-free, distant metastasis-free and cause-specific survival rates were 96.6%, 94.8%, and 99.1%, respectively. Conclusions This analysis showed lower vaginal late toxicity rate in C2 compared to C1.

Background Sarcopenia is defined as depletion in lean muscle mass with a loss of muscle strength and has been associated with increased morbidity and mortality in chronic diseases. Despite the risks and potential consequences of low lean muscle mass in patients with Crohn’s disease (CD), the impact of sarcopenia has been poorly evaluated. Therefore, the aim of our study was to assess the role of sarcopenia in predicting clinical and endoscopic outcomes in a cohort of CD patients. Methods Consecutive CD patients who started biologics between, 2015 and, 2020 and who underwent abdominal magnetic resonance imaging (MRI) within, 6 months from the beginning of the treatment were enrolled. Sarcopenia was defined as sex-specific total psoas area index (TPAI), measured at the, 3rd lumbar vertebra level, below the, 25th percentile. Multivariate analysis was used to evaluate whether sarcopenia could predict steroid-free clinical remission (Harvey-Bradshaw Index [HBI] Results 358 patients were included. Sarcopenic patients were older (p = 0.001), with lower body mass index (BMI) (p = 0.001) and higher Charlson Comorbidity Index (p = 0.02). Furthermore, sarcopenia was associated with a lower rate of endoscopic response (p = 0.014) and a lower SES-CD and Rutgeerts score after, 52 weeks of treatment (p = 0.008; p = 0.001). In multivariate analysis, sarcopenia was an independent predictor of absence of endoscopic response (odds ratio [OR] = 2.8;, 95% confidence interval (95% CI), 1.1–7.5; p = 0.02), along with smoking (OR = 2.39;, 95% CI, 1.05–5.44; p = 0.038) and perianal disease (OR = 2.69;, 95% CI, 1.19–6.08; p = 0.017). Sarcopenia was not associated with steroid-free clinical remission. Conclusion This is the first study demonstrating that sarcopenia is a poor prognostic factor for endoscopic response in CD patients. These results suggest that, in the future, screening for sarcopenia on routine abdominal MRI could be used in clinical practice for better management of CD patients in need of biological therapy. Further studies with a larger sample size and a validation cohort are needed to confirm our data.

Background There is no head-to-head trial comparing ustekinumab (UST) and vedolizumab (VDZ) in Crohn’s disease (CD). Recently, real-world studies evaluated the two biologics in patients refractory to anti-TNF therapy, i.e. as second-line agents. Conversely, no study specifically focused on the effectiveness of UST and VDZ as third-line agents, i.e. after failure with at least one TNF-α inhibitor plus failure with VDZ or UST. We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ in these highly-refractory patients with CD. Methods Data of consecutive patients with CD treated with UST and VDZ as third-line therapy until October, 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). The effectiveness was evaluated at, 8, 26, and, 52 weeks, and as treatment persistence at the end of follow up. The clinical outcomes were steroid-free clinical remission (SFCR - Harvey-Bradshaw Index Results 143 patients (UST: n=113; VDZ: n=30) were included. After, 8 weeks, SFCR was reported in, 38.1% of patients treated with UST and in, 43.3% of patients treated with VDZ (p=0.75), while CR was reported in, 61.9% of patients treated with UST and in, 60.0% patients treated with VDZ (p=1.00). After, 26 weeks, the rates of SFCR and CR were, 41.6% for UST and, 50.0% for VDZ (p=0.60), and, 61.4% for UST and, 66.7% for VDZ (p=0.81), respectively. After, 52 weeks, the rates of SFCR and CR were, 51.8% for UST and, 57.1% for VDZ (p=0.78), and, 65.9% for UST and, 71.4% for VDZ (p=0.77), respectively. Lack of difference in effectiveness between the two drugs at any time point was confirmed by multiple logistic regression models. After, 26 weeks, 88.7% of patients treated with UST and, 81.4% of patients treated with VDZ were still on treatment. Univariable Cox survival analysis showed a higher probability of treatment discontinuation for VDZ compared with UST (HR for VDZ:, 2.66; p=0.008), even if such difference was not confirmed at the multiple Cox proportional hazard regression model (HR for VDZ:, 1.94; p=0.08), where only age (HR, 0.98; p=0.04) and use of systemic steroids at baseline (HR, 3.29; p=0.003) were found to be independent predictors of treatment discontinuation. Conclusion This is the first real-world study assessing VDZ and UST as third-line therapy in patients with CD. Both drugs showed surprisingly high effectiveness, without significant differences between them.

BACKGROUND AND AIM There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naive to ADA and naive to anti-tumor necrosis factors; group B, naive to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P

Background/aim Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules. Patients and methods All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources. Results Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%. Conclusion cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.

Digital health (DH) is nowadays fundamental for physicians. Despite the improvement of information and communications technology (ICT), Italian medical doctors' (MDs) education system seems inadequate in this area. Moreover, due to the COVID-19 pandemic, societies are waking up to their limitations. The aim of this paper is to analyze the Italian status quo in DH.The Italian Young Medical Doctors Association (Segretariato Italiano Giovani Medici - SIGM) proposed a web-based survey to assess DH awareness and previous knowledge among young doctors. Investigated areas were: big data, -omics technology and predictive models, artificial intelligence (AI), internet of things, telemedicine, social media, blockchain and clinical-data storage.A total of 362 participants answered to the survey. Only 13% had experience in big data during clinical or research activities, 13% in -omics technology and predictive models, 13% in AI, 6% had experience in internet of things, 22% experienced at least one telemedicine tool and 23% of the participants declared that during their clinical activities data collection was paper-driven.Three categories of MDs, high-tech, low-tech and no-tech, can be identified from the survey-based investigation. Our survey's results indicate an urgent need for integration of pre- and post-graduation training in digital health to provide adequate medical education.

Purpose: Orbital pseudotumor (or pseudotumor orbitae) is a benign entity, also known as idiopathic orbital inflammatory syndrome (IOIS), which encompasses a wide range of non-tumoral, space occupying lesions of the orbit. In selected cases of refractory disease or presence of side effects or even comorbidities that limit systemic therapies, radiotherapy could play a role in the management because it has been demonstrated that irradiation is effective in suppressing the inflammatory process. Methods: A systematic review of the literature about the main scientific databases was launched and the time interval included all published articles present in the databases from their inception until September 2020. Results: We were able to identify 19 studies eligible for inclusion in this review from 1978 to 2018. Overall the data of 241 patients were collected and are presented in this systematic review. The response rate varied between 74% and 100% with a median recurrence rate of 10%. The median total dose was 20 Gy whereas the mean total dose was 21 Gy with a range from 4 to 36 Gy. Regarding the fractionation, 2 Gy/fraction daily was the most widely used. Conclusions: Radiotherapy seemed to achieve good response rates however, in most of the studies, inclusion criteria and outcome parameters are not uniform and therefore the results are difficult to compare. Often important parameters such as chronic pain and permanent functional deficits are not assessed in the outcome. Therefore, prospective studies, with good cohort characteristics and a clear definition of the outcome, are required.

PurposeDistant metastases are currently the main cause of treatment failure in locally advanced rectal cancer (LARC) patients. The aim of this research is to investigate a correlation between the variation of radiomics features using pre- and post-neoadjuvant chemoradiation (nCRT) magnetic resonance imaging (MRI) with 2 years distant metastasis (2yDM) rate in LARC patients.Methods and MaterialsDiagnostic pre- and post- nCRT MRI of LARC patients, treated in a single institution from May 2008 to June 2015 with an adequate follow-up time, were retrospectively collected. Gross tumor volumes (GTV) were contoured by an abdominal radiologist and blindly reviewed by a radiation oncologist expert in rectal cancer. The dataset was firstly randomly split into 90% training data, for features selection, and 10% testing data, for the validation. The final set of features after the selection was used to train 15 different classifiers using accuracy as target metric. The models’ performance was then assessed on the testing data and the best performing classifier was then selected, maximising the confusion matrix balanced accuracy (BA).ResultsData regarding 213 LARC patients (36% female, 64% male) were collected. Overall 2yDM was 17%. A total of 2,606 features extracted from the pre- and post- nCRT GTV were tested and 4 features were selected after features selection process. Among the 15 tested classifiers, logistic regression proved to be the best performing one with a testing set BA, sensitivity and specificity of 78.5%, 71.4% and 85.7%, respectively.ConclusionsThis study supports a possible role of delta radiomics in predicting following occurrence of distant metastasis. Further studies including a consistent external validation are needed to confirm these results and allows to translate radiomics model in clinical practice. Future integration with clinical and molecular data will be mandatory to fully personalized treatment and follow-up approaches.

Objectives The aim of this paper was to conduct a survey about the evolution of the information provided by Italian radiotherapy departments with a special focus on patients’ perspective. Methods A two-steps analysis was conducted in 2013 and 2020. Starting from analysis of data for the existing websites of Italian radiotherapy departments, main potential areas of interest for patients were discussed within a dedicated multidisciplinary team composed of radiation oncologists, a web designer, a blogger, a psyco-oncologist, a volunteer and a representative of patients’ association. Results Six patient-oriented features to evaluate the websites of Italian radiotherapy departments were identified and several other features not specifically patient-oriented were also reported in our survey. Conclusions A major effort is still needed to develop websites intended to be used by patients which should be both user-friendly and easily accessible. Social media are rapidly gaining a growing importance. Practice implications A pivotal role could be played by patients’ organization who should be empowered by connecting all the stakeholders involved in this field.

The mountain chain of the Alps, represents the habitat of alpine fauna where the red deer (Cervus elaphus) population is the outmost numerous, followed by the chamois (Rupicapra rupicapra) and the alpine ibex (Capra ibex) at higher altitudes. Previous reports showed the circulation of epitheliotropic viruses, belonging to the families Papillomaviridae and Poxviridae, causing skin and mucosal lesions in wild ruminants of the Stelvio National Park, situated in the area. To deepen our knowledge on the natural dynamics of the infections, a passive surveillance on all the cases of proliferative skin and mucosal lesions in wild ruminants was performed. Twenty-seven samples (11 chamois, 10 red deer and 6 ibex) collected from 2008 to 2018 were analyzed by negative staining electron microscopy, histology, and PCR followed by genome sequencing and phylogenetic analyses. Results confirmed the spread of Parapoxvirus of Red Deer in New Zealand (PVNZ) in Italy, and its ability to cause severe lesions i.e., erosions and ulcers in the mouth. We showed for the first time a PVNZ/CePV1v (C. elaphus papillomavirus 1 variant) co-infection identified in one red deer. This result supports previous evidence on the ability of papillomavirus and parapoxvirus to mutually infect the same host tissue. Interestingly two ibex and one chamois showing orf virus (OV) skin lesions were shown to be co-infected with bovine papillomavirus type 1 and 2. The presence of bovine papillomavirus, in orf virus induced lesions of chamois and ibex raises the question of its pathogenetic role in these animal species. For the first time, OV/CePV1v co-infection was demonstrated in another chamois. CePV1v is sporadically reported in red deer throughout Europe and is considered species specific, its identification in a chamois suggests its ability of cross-infecting different animal species. Poxviruses and papillomavirus have been simultaneously detected also in the skin lesions of cattle, bird and human suggesting a possible advantageous interaction between these viruses. Taken together, our findings add further information on the epidemiology and pathogenetic role of epitheliotropic viruses in wild ruminants living in the central Alps and in Stelvio National Park.

The aim of this study was to evaluate the variation of radiomics features, defined as “delta radiomics”, in patients undergoing neoadjuvant radiochemotherapy (RCT) for rectal cancer treated with hybrid magnetic resonance (MR)-guided radiotherapy (MRgRT). The delta radiomics features were then correlated with clinical complete response (cCR) outcome, to investigate their predictive power. A total of 16 patients were enrolled, and 5 patients (31%) showed cCR at restaging examinations. T2*/T1 MR images acquired with a hybrid 0.35 T MRgRT unit were considered for this analysis. An imaging acquisition protocol of 6 MR scans per patient was performed: the first MR was acquired at first simulation (t0) and the remaining ones at fractions 5, 10, 15, 20 and 25. Radiomics features were extracted from the gross tumour volume (GTV), and each feature was correlated with the corresponding delivered dose. The variations of each feature during treatment were quantified, and the ratio between the values calculated at different dose levels and the one extracted at t0 was calculated too. The Wilcoxon–Mann–Whitney test was performed to identify the features whose variation can be predictive of cCR, assessed with a MR acquired 6 weeks after RCT and digital examination. The most predictive feature ratios in cCR prediction were the L_least and glnu ones, calculated at the second week of treatment (22 Gy) with a p value = 0.001. Delta radiomics approach showed promising results and the quantitative analysis of images throughout MRgRT treatment can successfully predict cCR offering an innovative personalized medicine approach to rectal cancer treatment.

Introduction: Pancreatic cancer (PC) is one of the most aggressive tumours, and better risk stratification among patients is required to provide tailored treatment. The meaning of radiomics and texture analysis as predictive techniques are not already systematically assessed. The aim of this study is to assess the role of radiomics in PC. Methods: A PubMed/MEDLINE and Embase systematic review was conducted to assess the role of radiomics in PC. The search strategy was ‘radiomics [All Fields] AND (“pancreas” [MeSH Terms] OR “pancreas” [All Fields] OR “pancreatic” [All Fields])’ and only original articles referred to PC in humans in the English language were considered. Results: A total of 123 studies and 183 studies were obtained using the mentioned search strategy on PubMed and Embase, respectively. After the complete selection process, a total of 56 papers were considered eligible for the analysis of the results. Radiomics methods were applied in PC for assessment technical feasibility and reproducibility aspects analysis, risk stratification, biologic or genomic status prediction and treatment response prediction. Discussion: Radiomics seems to be a promising approach to evaluate PC from diagnosis to treatment response prediction. Further and larger studies are required to confirm the role and allowed to include radiomics parameter in a comprehensive decision support system.

Background Clinical data on the use of Adalimumab (ADA) biosimilar ABP 501 in inflammatory bowel disease (IBD) are lacking. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) treated with ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled. Patients were divided into 3 groups (group A: naive to ADA and naive to anti-TNFs; group B: naive to ADA and previously exposed to anti-TNFs; group C: switch from ADA originator to ABP 501). The primary end-point was the assessment of safety, in terms of rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of clinical response and steroid-free clinical remission at 12 weeks for group A and B, and as treatment persistency for all 3 groups. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included [group A: 189 (33.8%); group B: 30 (5.4%); group C: 340 (60.8]. Overall, the mean follow-up was 8.7 months (median 10.0 months, interquartile range: 6.0–12.0 months), and the total follow-up time was 403.4 patient-years. 36 SAEs occurred in 36 patients (6.4%), with an incidence rate of 8.9 per 100 person-years (PY), and 22 of them caused the withdrawal of the drug (incidence rate: 5.5 per 100 PY). The incidence rate of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; incidence rate ratio=3.61; p Conclusion This is the first prospective study on the use of ADA biosimilar ABP 501 in IBD. Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Background The efficacy of Ustekinumab (UST) on Crohn’s disease (CD) associated spondyloarthropathy (SpA) was evaluated neither in randomized controlled trials nor in real-world studies. Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a multicentre, real-world assessment of the effectiveness of UST on CD-associated SpA Methods All consecutive CD patients with active SpA at the initiation of the treatment with UST from January 2019 (the date on which the drug became available for clinical practice in Sicily) to August 2019 were extracted from the SN-IBD cohort. The study outcomes were evaluated at 8 and 24 weeks. The primary outcome was the articular response, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. As ancillary end-points, the clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline with a concomitant reduction of at least ≥ 50% of steroid dosage compared with baseline) and the steroid-free remission (Harvey-Bradshaw Index < 5 without steroids use) were assessed. Results Out of 131 total patients treated with UST, 30 consecutive patients (22.9%) had active SpA at baseline (axial SpA: 3/30; peripheral SpA: 18/30; axial plus peripheral SpA: 9/30). After 8 weeks, 10 patients (33.3%) reported an articular response [0/3 patients with axial SpA, 7/18 patients (38.9%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. After 24 weeks, 13 patients (43.3%) had an articular response [0/3 patients with axial SpA, 10/18 patients (55.5%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. None of these 13 responders was taking systemic steroids at 24 weeks. The concomitant presence of a clinical response on intestinal symptoms was associated with the articular response at 24 weeks at univariable analysis (OR 5.14, CI 1.09-32.70, p=0.038). Conclusion UST obtained a response on articular symptoms in nearly half of the patients with CD and active SpA at baseline after 24 weeks. The rate of response was higher in case of peripheral arthropathy. The articular response was associated with the clinical response on intestinal symptoms.