Italian Institutions Research Articles

Surgery or Comorbidities: What Is the Primum Movens of Kidney Dysfunction After Nephrectomy? A Multicenter Study in Living Donors and Cancer Patients.

Background and Hypothesis: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are significant risks for kidney cancer (KC) patients undergoing partial (PN) or radical nephrectomy (RN) and for living kidney donors (LKD). This study compares AKI and CKD incidence in these groups with a pre-operative glomerular filtration rate (GFR) over 60 mL/min/1.73 m2. Methods: This study included 465 KC patients with cT1-2N0M0 kidney mass and 256 LKD who underwent nephrectomy at four Italian institutions from 2014 to 2021. Data on demographics, comorbidities, and therapies were analyzed. Serum creatinine and estimated GFR (eGFR) were measured before and after surgery. Outcomes were AKI (per KDIGO guidelines) and CKD stage progression. Analyses included descriptive statistics, ANOVA, logistic regression, and Kaplan-Meier survival. Results: Among 721 patients, significant age and gender differences were noted. Hypertension (41%) and diabetes (7.1%) were prevalent in RN and PN groups. Post-surgery AKI was more common in donors (84%), while CKD stage progression varied by surgery type (CKD stage G3 after 60 months: RN 48.91%, PN 18.22%, LKD 26.56%). Age, pre-surgery CKD, and surgery type predicted CKD progression. Limitations include retrospective design and bias. Conclusions: Both LKD and KC patients face similar AKI and CKD risks. Surgery type significantly influences AKI and CKD incidence, highlighting the importance of approach.

Active offer of influenza vaccination during hospitalization: a multicenter study in Sicily (Italy)

Abstract Background Every cold season, the Italian health institutions strongly recommend influenza vaccination for categories at risk of complications, however influenza vaccination coverage is over and over far from the desirable target of 95%. After the pilot experience conducted in Palermo during the 2022-23 influenza season, the ‘Vaccinations in the ward’ project was extended to other Sicilian centers in order to evaluate the impact of the vaccination offer strategy in a broader territorial reality and to analyze the determinants of influenza vaccine acceptance among at risk people. Methods The project was conducted at the Umberto I Hospital in Enna and the University Hospitals of Messina and Palermo during the 2023-24 influenza season. A questionnaire was administered to the at risk hospitalized patients to investigate socio-demographic factors, behavioral habits, and clinical condition. Furthermore, influenza vaccination upon discharge was offered. Multivariable logistic regression was performed to identify the determinants of influenza vaccine acceptance. Results Overall, 374 patients with a median age of 65 years (IQR: 50-70) were recruited, of whom 36% had been vaccinated for influenza during the 2022-23 season (n = 136). The patients who accepted influenza vaccination in the ward were 57% (n = 214). The determinants of vaccination adherence were: age (OR: 1.03; p = 0.003); having quit smoking (OR: 2.68; p = 0.017); having received advice on vaccination from general practitioner (OR: 4.9; p < 0.001) and hospital healthcare workers (OR: 7.3; p < 0.001). Conclusions The offer of vaccination in the ward effectively increased influenza coverage among categories at risk of complications. Furthermore, the adoption of correct behavioral habits and the promotion of influenza vaccination by healthcare personnel have played a decisive role in the vaccine acceptance process. These findings could be useful for planning future influenza vaccination campaigns targeted to at risk people. Key messages • Vaccination strategies are needed to increase influenza coverage among at-risk categories. Active offer of influenza vaccine upon discharge can effectively increase vaccination compliance. • The adoption of correct behavioral habits and the promotion of vaccination by healthcare personnel play a decisive role in the influenza vaccine acceptance process among at risk people.

ALICENET – an Italian network of automated lidar ceilometers for four-dimensional aerosol monitoring: infrastructure, data processing, and applications

Abstract. ​​​​​​​Vertically resolved information on aerosol particles represents a key aspect in many atmospheric studies, including aerosol–climate interactions and aerosol impacts on air quality and human health. This information is primarily derived by lidar active remote sensing, in particular with extensive networks currently in operation worldwide. In Italy, the Institute of Atmospheric Sciences and Climate (ISAC) of the National Research Council (CNR) established the ALICENET network of automated lidar ceilometers (ALCs) in 2015. Since then, ALICENET has grown as a cooperative effort of Italian institutions dealing with atmospheric science and monitoring, and it currently includes instruments run by regional environmental protection agencies, universities, research centres, and private companies. In the current configuration, the network makes use of both single-channel ALCs and dual-channel, polarisation-sensitive-system ALCs (referred to as PLCs). The systems operate in very different environments (urban, coastal, mountainous, and volcanic areas) from northern to southern Italy, thus allowing the continuous monitoring of the aerosol vertical distribution across the country. ALICENET also contributes to the EUMETNET programme E-PROFILE, filling an Italian observational gap compared to other EU member states, which generally run extended ALC networks through national meteorological services. In this work, we present the ALICENET infrastructure and the specifically developed data processing centralised at CNR-ISAC, converting raw instrumental data into quantitative, quality-controlled information on aerosol properties ranging from attenuated backscatter to aerosol mass and vertical stratifications. This setup allows us to get insights into the 4D aerosol field over Italy with applications from near-real-time monitoring to long-term analyses, examples of which are reported in this work. Specific comparisons of the ALICENET products to independent measurements obtained with different techniques, such as particulate matter (PM) concentrations from in situ samplers and aerosol optical depth (AOD) from sun photometers, are also included here, revealing the good performances of the ALICENET algorithms. Overall, ALICENET represents a valuable resource to extend the current aerosol observational capabilities in Italy and in the Mediterranean area, and it contributes to bridging the gap between atmospheric science and its application to specific sectors, among which are air quality, solar energy, and aviation safety.

Gli spazi di accoglienza multireligiosa nel sistema universitario italiano

Multi-religious Welcoming Spaces in the Italian University System ABSTRACT: The essay deals with the issue of the spaces Italian universities provide for worship and other spiritual activities. Designating public spaces for religious and spiritual needs is an example of the ongoing adaptation process of institutions to social needs that is marked by ever-increasing religious and cultural pluralism. However, Italian universities have been affected by this phenomenon only in a marginal way so far. This paper, which is based on field research, describes the similarities and differences of the solutions adopted in various Italian institutions of higher education. In her concluding remarks, the Author points out the emergence of the “Islamic Question”. Indeed, the attitude towards Muslim communities by Italian universities is very similar to that of other public administrations. SOMMARIO: 1. Introduzione: pluralismo religioso e identità nella comunità studentesca universitaria italiana - 2. Gli spazi universitari di accoglienza della diversità religiosa - 3. Stanze multireligiose nel sistema universitario italiano: unapreliminare e frastagliata mappatura - 4. L’accoglienza multireligiosa nel sistema universitario: uno specchio delle dinamiche italiane fra Stato e confessioni religiose? Brevi conclusioni.

Locating Anglo-Italian Communities in Bevis and the Naples Manuscript

This article contextualises the Anglo-Italian aspects of Naples, Biblioteca Nazionale, MS XIII.B.29. This fifteenth-century paper miscellany contains Bevis of Hampton, Chaucer’s Clerk’s Tale, St Alexius, Libeaus Desconus, as well as a recipe collection, a section of Lydgate’s “Doublenesse”, and a fragment of Sir Isumbras. The book is among a very select number of codices containing Middle English texts that are presently preserved in an Italian institution. Previous research has demonstrated XIII.B.29 must have travelled to the Italian peninsula at a relatively early date, but the exact reason behind its compilation and the method by which it arrived in Italy remain uncertain. This article reviews the manuscript’s design, provenance, and contents, arguing the book is not just an English manuscript in Italy, but also to some degree an English manuscript about Italy and Italian experiences. Specifically, the article contends that an episode in the manuscript’s Bevis, which describes a street fight near Lombard Street in London, benefits from a reading that acknowledges late medieval developments in finance and long-distance Anglo-Italian commerce, as well as the emergence of Italian communities in Southampton and the capital.

Late Colonialism and Postcolonial Development in Africa: A Comparative-Historical Analysis of Former Italian Africa

This article analyzes the development legacies of Italian colonialism in Africa. The comparative-historical analysis shows that colonial Italy pursued “settler colonialism” in areas conducive to colonial settlement and large-scale exploitation, and “plantation colonialism” in areas with fewer resource endowments and settlement opportunities. In the immediate aftermath, while settler colonialism had a positive influence and plantation colonialism exerted a negative impact on economic prosperity, both types of Italian colonialism had strong negative effects on human development. In the post-1960 period, whereas the colonial legacy of plantation colonialism led to persistent poverty in Somalia, long-run development in Eritrea and Libya was contingent on critical junctures, which variously reinforced, destabilized, and/or transformed the institutional and developmental legacies of settler colonialism. I draw on the comparative-historical tradition emphasizing national orientation of European colonizers and natural conditions in colonized areas as key determinants of European colonialism and long-run development. However, I emphasize “factor endowments” as one such condition that defined Italian colonization strategies and institutions, finding little empirical support for factor endowments per se or precolonial ethnic centralization as principal determinants.

The top 100 most-cited articles in dentistry by authors with Italian affiliation.

Analyzing highly-cited articles can provide a retrospective assessment of research evolution and predict future developments. The aim of this study was to carry out a bibliometric analysis of the 100 most-cited articles in dentistry by authors with an Italian affiliation. All the articles published in journals indexed under the Scopus category "Dentistry" and with at least one author affiliated to any Italian institution were searched in September 2022. The 100 most-cited articles were selected and relevant data were extracted and summarized. The analysis of co-authorship at country level and co-occurrence of keywords was carried out. The 100 most-cited articles were published between 1976 and 2020. The number of citations ranged from 235 to 1683, with a mean of 361. The series included 25 citation classics (>400 citations). The majority of articles were classified as expert opinion/narrative reviews (N.=47). Almost half of the articles refer to three predominant disciplines which were implantology, periodontology and restorative dentistry. Only two articles were single-authored. In 30 articles, all the authors had an Italian affiliation and the US was the most frequent country for non-Italian authors. Only one article was published in journals owned by a non-Italian publisher. The present series of highly-cited articles confirms the important role of Italy in dental research. We found an absence of correlation between the level of evidence and the number of citations and a non-homogeneous distribution of highly-cited papers in the different dental disciplines. The majority of articles included in the series shared international co-authorship and were published in high-impact journals.

Digital object-based learning for people with ASD: a training experience within heritage education contexts

The paper aims at presenting a training experience for future educators carried out during the academic year 2022/2023 on the use of Digital Object-Based Learning (OBL) for people with Autism Spectrum Disorders. Three different webinars, designed within the Erasmus+ Spektrum project, have been realised with a focus on the design, implementation, and evaluation of personalised museum educational experiences to foster social inclusion and wellbeing within people with specific educational needs through Object-based learning (OBL). As stated by the literature in the field, hands-on learning within heritage education contexts can really enhance people's interest in and understanding of a topic/subject and develop important transverse skills, thus promoting cultural participation of users at risk of social exclusion. During the webinars, specific models for planning learning sessions with ASD people were presented, together with wellbeing and empathy assessment tools to be used within museum context. The training experience ended with a digital OBL session, where museum educators were asked to collaboratively analyse, interpret, and evaluate digitised museum objects. More than 90 in-training educators, from different Italian and Spanish institutions, attended the webinars: results from a final assessment survey are presented in order to highlight strengths and weaknesses of the training experience, the soft and hard skills most promoted and the educational needs of the participants, trying to identify challenges and potential transformations within digital heritage education context.

International cross-sectional survey on attitudes and practices regarding use of contrast-enhanced ULTRAsound in VASCular surgery: The I-ULTRA-VASC study.

The aim of this cross-sectional survey was to gather attitudes and practices of physicians from different countries regarding the implementation of contrast-enhanced ULTRAsound (CEUS) for vascular diseases in clinical practice as well as in academic research. A web-based survey was developed in English, including 35 questions. Two-hundred sixty physicians were invited by email to fill in the survey anonymously on Google Forms using a dedicated link. The survey started on 25th February 2024 and was closed on 13th March 2024 (17days). A reminder was sent after the first 10days. In addition to descriptive statistics, sub-analyses of answers according to country of origin (Italy vs other States), years of experience (≤20years vs > 20years), and type of institution (Academic/University vs Non-Academic/Private) were also established a priori. A total of 121 practitioners from 20 countries completed our survey (response rate 121/260, 46%). Most responders were males (95/121, 78.5%). Most participants were vascular surgeons (118/121, 97.5%). CEUS was available in 87/121, 70.2% of the centers involved, even though a standardized protocol was present in 54/121, and 44% of surveyed institutions. Italian institutions presented greater CEUS availability (62/72, 86.1% vs 25/49, 51.0%; p = .001) and higher presence of standardized protocols (38/72, 52.8% vs 16/49, 32.6%; p = .022) than foreign institutions. The diagnostic tool was thought to be more useful for carotid artery stenosis in the postoperative phase, while for abdominal aortic aneurysms (AAAs) in the preoperative phase. For diagnosis and/or preoperative management of carotid stenosis 53/121, 44% of physicians believed that CEUS should be performed only in selected cases, while for AAA 42/121, 35% of them believed that it could be useful only for scientific purposes. Similarly, 99/121, 82% of participants answered that CEUS was usually prescribed in 0%-20% of the cases during the preoperative diagnostic pathway of patients with peripheral arterial disease. No differences between country of origin, years of experience, and type of institution were found for the reported items. There was also 106/121, 88% of respondents agreed upon the need for better integration of CEUS in current guidelines and 114/121, 94% of them upon the need for further studies. This ULTRA-VASC survey has demonstrated that CEUS is still rarely used in current practice for many vascular diseases despite the availability of this tool in most centers Future studies are needed, as well as enhanced guidance on the proper implementation of CEUS from guidelines.

The prognostic role of MRI-based radiomics in tongue carcinoma: a multicentric validation study

PurposeRadiomics is an emerging field that utilizes quantitative features extracted from medical images to predict clinically meaningful outcomes. Validating findings is crucial to assess radiomics applicability. We aimed to validate previously published magnetic resonance imaging (MRI) radiomics models to predict oncological outcomes in oral tongue squamous cell carcinoma (OTSCC).Materials and methodsRetrospective multicentric study on OTSCC surgically treated from 2010 to 2019. All patients performed preoperative MRI, including contrast-enhanced T1-weighted (CE-T1), diffusion-weighted sequences and apparent diffusion coefficient map. We evaluated overall survival (OS), locoregional recurrence-free survival (LRRFS), cause-specific mortality (CSM). We elaborated different models based on clinical and radiomic data. C-indexes assessed the prediction accuracy of the models.ResultsWe collected 112 consecutive independent patients from three Italian Institutions to validate the previously published MRI radiomic models based on 79 different patients. The C-indexes for the hybrid clinical-radiomic models in the validation cohort were lower than those in the training cohort but remained > 0.5 in most cases. CE-T1 sequence provided the best fit to the models: the C-indexes obtained were 0.61, 0.59, 0.64 (pretreatment model) and 0.65, 0.69, 0.70 (posttreatment model) for OS, LRRFS and CSM, respectively.ConclusionOur clinical-radiomic models retain a potential to predict OS, LRRFS and CSM in heterogeneous cohorts across different centers. These findings encourage further research, aimed at overcoming current limitations, due to the variability of imaging acquisition, processing and tumor volume delineation.

The current scenario of clinical ethics in Italy

Background: Italy has seen limited growth and institutionalization of clinical ethics activities in its territory. Only a few observational studies were conducted in Italy to assess the state of the art of clinical ethics services and activities. Aim: We sought to gain a broad and comprehensive understanding of the state of the art as perceived by Italian healthcare institutions and facilities. Methods: We prepared a questionnaire comprising of twelve close-ended and six open-ended questions. We sent it to all Local Healthcare Authorities (Aziende Sanitarie Locali, ASL), all private Scientific Institutes for Research, Hospitalization and Healthcare (Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS), and all hospices throughout Italy. Out of 380 facilities, 90 of them (22.5%) responded to it. Results: All answers revealed interesting data. Among them, the ones that stood are: when asked who they turn to when an ethical dilemma arises, 27.7% of the respondents checked more than two answers, thus showing that there is not one clear and unequivocal body of reference. When asked if there are standard procedures, 55.4% of the respondents declared that there are no standard procedures. Only 4.4% of respondents declared the method of analysis being used. 53.3% responded that their hospital or healthcare facility does not regularly offer training activities and formation to deal with ethical dilemmas Conclusion: The three topics that stand out are a great fragmentation, the need to formalize and establish dedicated services to take care of ethical dilemmas and to offer training and formation to healthcare providers.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

Adjuvant endocrine therapy choices in premenopausal patients with hormone receptor-positive early breast cancer: Insights from the prospective GIM23-POSTER study

BackgroundMost premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methodsThe Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. ResultsBetween October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. ConclusionsAI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.

Mental distress and well-being in geriatric professionals: The role of job satisfaction

BackgroundAs limited evidence is available on health professionals’ experience during the post-pandemic period, the interplay between job satisfaction components, mental distress and well-being was investigated among workers of an Italian geriatric institution. MethodsIn Spring 2022, 205 participants (females =75.6%), primarily healthcare assistants (36.6%), nurses (16.6%), and rehabilitation professionals (14.1%), completed the General Health Questionnaire (GHQ), the Mental Health Continuum-Short Form (MHC-SF), and the Job Satisfaction Questionnaire. Data analyses comprised Multiple Regressions, Relative Weight Analyses, and ANOVA. FindingsSatisfaction with working conditions and leadership exhibited negative associations with distress, while satisfaction with patients, colleagues, results, and leadership were positively correlated with well-being. Participants with high well-being levels scored significantly lower across mental distress dimensions than participants reporting poor well-being levels. ConclusionsResults showed that specific job satisfaction components relate differently to distress and well-being, suggesting the need for implementing organizational resources, psychological support, and interprofessional collaboration in healthcare services.

A Technical-Thematic Civil Protection Exercise in Italy: UAS Fleets-Based Activities Supporting Emergency Response in Seismic Scenarios

In October 2023, during the Italian Civil Protection Week, in Eastern Lombardy (Italy) a large technical-thematic seismic exercise called “EXE.Lomb.Est 2023” was organized, with the goal of testing the response of the Regional Civil Protection system for post-earthquake damage assessment activities. Within this context, the use of an unmanned aerial system (UAS), in particular the deployment of multi-rotors UAS teams, has been tested as support for the rapid mapping of a large area involving the simultaneous participation of different Italian institutions with UAS units. Coordinated flight planning design, safety issues, coordination and communication procedures, data management and delivery of the results are some of the main aspects investigated and presented in this work.

Foreign travellers in Milan and their interests

Abstract This article reviews the presence and movements of foreign travellers in Milan in the mid-nineteenth century, focusing on the cultural context of art collecting. Perceptions of the Milan region abroad are examined through a number of guides and illustrated digests aimed at foreign visitors and produced by local publishers such as Giovanni Pietro Giegler, Ferdinando Artaria, Bettalli and Vallardi. Along with the main landmarks, the importance of private palaces and their art galleries has also been researched. Among them are locations associated with some established names (the Archinto, Litta, Borromeo and Trivulzio families), as well as new entries such as the Poldi Pezzoli family. The sections of guidebooks devoted to the city’s antiquarian market were particularly significant within these publications, a study of which helps us to understand the unexpected dynamics of some emerging antique dealers’ careers. Emphasis is placed on case-studies, notably the important and remarkable example of Alfonso Reichmann, whose family owned a famous hotel at Porta Romana. Reichmann successfully engaged in the domestic and international art trade, dealing with foreign museums as well as with Italian institutions and collectors, including Gian Giacomo Poldi Pezzoli.

The role of metastasectomy in patients with early onset metastatic colorectal cancer.

3541 Background: According to the literature, metastasectomies in colorectal cancer patients can lead to a significant increase in outcomes. However, the behavior of early-onset CRC (EO-CRC), which refers to cancer occurring in adults between 18 and 49 years, when subjected to metastasectomy, remains unclear. Clinical and prognostic data on this setting are limited and conflicting. Our study aimed to evaluate clinical, prognostic, and molecular differences in early-onset colorectal cancer (EO-CRC) patients undergoing metastasectomy to identify potentially relevant differences compared to a control group of late-onset CRC (LO-CRC). Methods: We retrospectively collected data from 1123 metastatic colorectal cancer patients from 5 different Italian Institutions. 673 (59.9%) EO-CRC and 450 (40.1%) LO-CRC as a control group. All patients had one or more metastatic sites, molecular profiling available (including RAS, BRAF, and MSI status), and underwent at least one line of treatment for metastatic disease. The main objective of the study was to evaluate clinical outcomes for the EO-CRC patients undergoing metastasectomy in comparison to patients included in the control group according to molecular profile. Results: In the EO-CRC group, the median age was 44.1 (20.0-50.9), while in the control group, it was 64.4 (51.0-86.2). Among EO-CRCs patients, 388 out of 673 (57.6%) underwent metastasectomy, whereas, in LO-CRCs patients, only 181 out of 450 (40.2%) had the procedure. In the general population, patients who underwent metastasectomy demonstrated a higher median overall survival (mOS) compared to those who did not undergo the procedure. However, within the metastasectomy group, EO-CRCs patients exhibited a lower mOS compared to LO-CRCs patients (46.0 versus 60.0 months, p &lt; 0.0001). Similar results were obtained when evaluating subgroups of RAS-BRAF wild type patients (53.0 months versus 81.0 months, p &lt; 0.0001) and RAS-BRAF mutated patients (42.0 months versus 45.0 months, p &lt; 0.0001). Conclusions: Although EO-CRC patients seem more likely to undergo surgical resection for metastatic disease, our findings suggest a worse overall prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly, this seems to occur regardless of the molecular status. These observations could have a considerable impact on clinical practice and research. Further investigations will be necessary to better understand the specific clinical and molecular characteristics of this growing group of patients to better define the most appropriate therapeutic strategy.

Clinical outcomes and impact of mismatch repair deficiency (dMMR) in patients with pT4N0 colon cancer (CC): Data from a large, consecutive, multicenter, real-world cohort.

3619 Background: T4 is widely recognized as one of the most important and independent prognostic factors in adjuvant setting for CC patients. However, the optimal management in terms of adjuvant treatment in stage II (pT4N0) as well as the impact of DNA mismatch repair deficiency (dMMR) in this subset of patients remain unclear. Here, we present a large, multicenter, real-world analysis of pT4N0 CC patients. Methods: A real-world database including pts treated at 9 Italian institutions from April 2010 to November 2023 was queried. Clinico-pathological characteristics of pts diagnosed with a stage II pT4N0 CC were analyzed. Pts were stratified according to duration of treatment, DNA mismatch repair (MMR) status, type of adjuvant chemotherapy (ACT). The primary endpoints were median relapse-free survival (RFS) and overall survival (OS). Results: A total of 380 pts was included, and outcomes data were available for 288 pts.Median age was 73 years and 49% of pts were male. 47 pts (16%) had dMMR CC, among which Lynch Syndrome was diagnosed in 19%. 10% of pts had BRAF mutant tumor, and 38% KRAS mutant tumor. After a median follow-up of 40.6 months (37.9-49.3), 3-yr RFS and 5-yr RFS were 70% and 55%, respectively, regardless treatment; 3-yr OS was 88% and 5-yr OS 73%. 154 pts (53%) received ACT: oxaliplatin (oxa)-based CT was given to 103 pts (67%), compared to 51 pts who received monotherapy (33%). Six-month ACT was given to 38 pts (74.5%) and 75 pts (72.8%) in the monotherapy and oxa-based group, respectively. Pts receiving 6-month ACT had a significant longer OS compared to those who did not receive ACT (HR 0.17; 0.08-0.34; p &lt;.001). A trend towards improved OS was observed in pts receiving 6-month ACT versus pts receiving 3-month ACT (HR 0.46; 0.16-1.29; p 0.129). Similar results were observed in terms of RFS: 6-month ACT showed a longer RFS compared to 3-month ACT (HR 0.58; 0.32-1.05; p .068), and a significantly longer RFS compared to no-ACT (HR 0.50; 0.32-0.77; p .001). Oxa-based ACT was associated with a significant improvement in OS compared to monotherapy (HR 0.30; 0.11-0.85; p .016). Overall, pts with dMMR CC did not show a statistically significant difference in terms of OS and RFS (p .66 and .19 respectively) compared to proficient MMR pts. Conclusions: In this large real-world dataset, T4 was confirmed being a key poor prognostic factor, independently to MMR status. We observed that ACT provides large benefit in this population, and oxa-based ACT may be better than monotherapy. In addition, 6-month oxa-based ACT showed a trend towards a better outcome in comparison to 3-month ACT, even if not statistically significant. Given the retrospective nature of the study, these data should be validated in larger and prospective cohorts; however, this work may help oncologists in shared decision making in this specific subgroup of patients.

Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers.

Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents. We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group. Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; P = .95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; P = .4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; P = .9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, P = .27). HR-/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.

Chemotherapy Rechallenge or Reintroduction Compared to Regorafenib or Trifluridine/Tipiracil for Pretreated Metastatic Colorectal Cancer Patients: A Propensity Score Analysis of Treatment Beyond Second Line (Proserpyna Study)

BackgroundThe optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated. Patients and methodsPROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses. ResultsData referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses. ConclusionsAlthough the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.