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Background: Financial toxicity from cancer treatments is rising as an important patient-reported outcome. Its relevance was first assessed in the context of privately financed healthcare system, where the financial hardship caused by out-of-pocket payments negatively affects survival, while fewer evidence exists on its role in countries where care is financed by the public health care system. Head and Neck Cancer (HNC) patients face an increased risk for financial toxicity due to multimodal treatment and relevant out of pocket costs. The aim of this study was to develop and validate an Italian version of the Canadian Financial Index of Toxicity (FIT) questionnaire, defined FITALY., Methods: FIT questionnaire was translated through a forward-backward process by two investigators independently, and the process was reviewed by a certified medical scientific English native speaker. Once reached consensus upon Italian translation, two Health Economics experts were consulted to adapt the questionnaire to Italian socio-economic context. The FITALY questionnaire v1.0 hereby developed was anonymously administered to two consecutive groups of 30 patients who had received curative, multimodal treatment for HNC cancer at ASST Spedali Civili of Brescia, Italy. A cognitive debriefing form was simultaneously administered to ask patients to exclude recurring and redundant items and include new relevant items., Results: The 14-item FITALY questionnaire provides a global evaluation of financial toxicity ranging from 0 to 100. The questionnaire is divided into 4 domains: financial burden (6 items), exploring the objective financial toxicity burden; financial distress (2 items), which refers to the psychological distress related to financial toxicity; out-of-pocket costs (4 items), which focus on medical expenses paid by the patient; and loss of productivity (2 items), that investigates the disease impact on both patient's and caregiver's job activity., Conclusions: Starting from the Canadian 9-item FIT questionnaire, we developed and validated the Italian 14-item FITALY questionnaire. Prospective application to a cohort of Italian HNC patients is ongoing., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethical Committee of ASST Spedali Civili of Brescia (NP 5560). According to this approval, informed Consent Form was not required for the procedure of questionnaire development and validation since patients participated anonymously and no patient data was collected. Patients were asked to provide personal insights and experience with financial toxicity, and to evaluate the intelligibility and the completeness of the questions and answers of the questionnaire. Consent for publication: No/Not applicable (this manuscript does not report data generation or analysis). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The oral factor Xa inhibitor, edoxaban, is effective and safe in cancer-associated Venous Thromboembolism (VTE) treatment. The EDOI study aims to evaluate compliance and quality of life (QoL) in patients with cancer-associated VTE treated with edoxaban during antineoplastic care., Material and Methods: The EDOI was a multicentre phase IV, single-arm study. Patients received edoxaban for at least 6 months. The primary objective was to evaluate the rate and 90 % Confidence Intervals of edoxaban-related adverse events (AEs) with impact on antineoplastic therapy in terms of delays, reduction, or interruption. Mixed models for repeated measure have been adopted to evaluate the secondary endpoint as the change of QoL scores from enrolment to 6 months., Results: From July 2019 to March 2021, 147 patients were enrolled. Edoxaban-related AEs with impact on antineoplastic therapy were observed in 7 patients (4.76 %; 90 %CI 2.23 %-8.94 %). The cumulative incidence of AEs was 2.7 % at 1 month from enrolment. A statistically significant increase (p < 0.05) was observed for mean changes in PACT-Q2 Convenience (+5 points) and Satisfaction (at least +2.5), and reduction of ACTS Burden (at least +1.7) at 1 month. Overall QoL measured by FACT-G shows a mean increase in the first month (+1.3), while decreases in the subsequent 5 months (-2.5)., Conclusion: The results of the EDOI Study demonstrate that edoxaban was well tolerated in patients receiving cancer treatment, showing a low rate of AEs with an impact on antineoplastic therapy, mainly within the first 30 days of administration. Lastly, the edoxaban-related AEs did not result in a lower overall QoL., Competing Interests: Declaration of Competing interest CP: outside the submitted work personal fees for the advisory role, speaker engagements, and travel and accommodation expenses from Amgen, Astellas, AstraZeneca, Bayer, Bristol Meyer Squibb, Celgene, Daiichi Sankyo, , Eisai, Ipsen, Janssen, Incyte, Merck-Serono, Merck Sharp and Dohme, Novartis, Roche, Sandoz, Sanofi, and Servier. AD: outside the submitted work, has received personal fees for the advisory role, speaker engagements, and travel and accommodation expenses from Ipsen, Servier, BMS, Merck Serono, Amgen, and Daichii Sankyo. MT: received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda, Amgen, Merck, Sanofi, Janssen, Daiichi Sankyo. M.T. received institutional research grants from Astra-Zeneca, Boehringer Ingelheim and Roche. M.T. received travel support from Amgen and Takeda. FaG: honoraria for Advisory board/Speaker's bureau: Servier, Eli Lilly, Bristol-Myers Squibb, Iqvia, Merck Serono, Amgen, Pierre-Fabre. MM: reports honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme (MSD), Novartis, Roche, Takeda, Viatris, Ipsen for consultancy or participation to advisory boards; direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche. Other authors have no COI.., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse., Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial were extracted (KN024 IPD cohort) to compare the long-term outcomes between the two cohorts. To further assess the reproducibility of clinical trial results, we reconstructed the "KN024 look-alike" cohort by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS)≥2, those requiring corticosteroids with doses ≥10 mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor receptor/anaplastic lymphoma kinase genotype, and those with pre-existing autoimmune disease. We additionally provided a hierarchical organization of determinants of long-term benefit through a conditional inference tree analysis., Results: The study included 1050 patients from 61 institutions across 14 countries, with a median follow-up of 70.3 months. The 5-year survival rate was 26.9% (95% CI: 23.8% to 30.2%), and median OS was 21.8 months (95% CI: 19.1 to 25.7), while 32 (3.0%) patients who achieved a complete response remained progression-free at the data cut-off. The KN024 look-alike cohort had a 5-year survival rate of 29.3% (95% CI: 25.5% to 33.6%) and a median OS of 27.5 months (95% CI: 22.8 to 31.3). Neither the overall study population nor the KN024 look-alike cohort exhibited significantly different OS compared with the KN024 IPD cohort. By the data cut-off, 1015 patients (96.7%) had permanently discontinued treatment: 659 (64.9%) due to progressive disease, 156 (15.4%) due to toxicity, 77 (7.6%) due to treatment completion, and 106 (10.4%) due to other reasons. Overall, 222 participants (21.1%) were treated for a minimum period of 24 months, among them the 5-year survival rates were: 31.7%, 72.7%, 78.6%, 84.2% for patients who discontinued treatment due to progressive disease, toxicity, treatment completion, and other reasons, respectively., Conclusion: This study provides valuable real-world evidence that confirms the long-term efficacy of pembrolizumab outside of clinical trials. Hierarchical organization indicates ECOG-PS, age and PD-L1-TPS as the most important predictors of 5-year survival, potentially informing clinical practice., Competing Interests: Competing interests: AC received grants for consultancies/advisory boards from MSD, BMS, OncoC4, IQVIA, AstraZeneca, REGENERON, Access Infinity, Ardelis Health, Alpha Sight, Guidepoint, Roche; speaker fees from AstraZeneca, Pierre-Fabre, MSD, Sanofi/REGENERON; payment for writing/editorial activity from BMS, MSD; travel support from Sanofi/REGENERON, MSD. JB declares honoraria/consulting or advisory role from AstraZeneca, BMS, Roche, Access Oncology, travel support from MSD, Roche, Janssen Oncology. GPS has received payment or honoraria for advisory boards from Novartis, Roche, Bayer, unrelated to this project. DO’R has received conference attendance support from Takeda, Janssen, Servier, MSD. EB has received grants or contracts from AstraZeneca, Roche and honoraria for lectures from Merck-Sharp & Dome, AstraZeneca, Pfizer, Eli-Lilly, Bristol Myers Squibb, Novartis, Takeda and Roche; EB has been member of Data Safety Monitoring Board or Advisory Board of Merck-Sharp & Dome, Pfizer, Novartis, Bristol Myers Squibb, AstraZeneca, Celltrion and Roche. AA declares consulting or advisory role for Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer, Eli Lilly, Astellas, Takeda, and Amgen; speaker’s bureau for Eli Lilly, and AstraZeneca. AR has received advisory board or speaker bureau honoraria from AstraZeneca, MSD, Novartis, Pfizer, BMS, Takeda, and Amgen; compensated activity for editorial projects from AstraZeneca, MSD, Novartis, Roche, and Regeneron. AL has received speakers’ fee for AstraZeneca, MSD, Sanofi and Takeda; he also received travel support from MSD and Novartis, has been on advisory board for AstraZeneca, BeiGene, Novartis and Sanofi, and has attended editorial activities sponsored by Eli Lilly and Roche. FM received honorary for advisory board roles with MDS, BMS, Takeda, Roche, AstraZeneca, Novartis. Paolo Bironzo served as consultant/advisory board for Regeneron, Pierre-Fabre, Janssen, Seagen. DO declares research funding/grants (to institution) from BMS, Merck, Palobiofarma, Pfizer, Genentech, AstraZeneca, Nuvalent, AbbVie, Onc.AI. TN-D received support to attend educational conferences from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche, Takeda; advisory roles for AbbVie, Amgen, Bayer, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli-Lilly, EQRx, Gilead, GSK, Janssen, Merck, MSD, Novartis, Novocure, Otsuka, Pfizer, Roche, Sanofi, Takeda; speaker bureau from Amgen, AstraZeneca, Chugai, Gilead, Janssen, Lilly, Medscape, Guardant, Merck, MSD, Roche, Takeda; trial steering committees’ member for AstraZeneca, Roche. BT received lecture fees from Pfizer. LC is an employee of Fortrea. BT declares honoraria from Roche. IM declares travel support from Takada, MSD, Pfizer, Oxyvie and speaker fees from Regeneron. A-MD declares research grants from Amgen, the Dutch Cancer Society and HANART, consulting fees from Amgen, Bayer, Boehringer Inglheim, Sanofy, Roche, Janssen and AstraZeneca, speaker fees from Janssen, Pfizer, AstraZeneca, Lilly and Takeda, advisory board role for Takeda and Roche. GLR declares fees for advisory boards, travel support, consultancies from MSD, BMS, Roche, Sanofi, Regeneron, Lilly, AstraZeneca, Janssen, Pfizer, Novartis, Bayer, Takeda, Amgen, GSK, Daichii. TAH declares stock interests for GlaxoSmithKline and honoraria from Novartis. BR served as consultant/advisory board for AMGEN, Regeneron, AstraZeneca, Capvision. Speaker fee: AstraZeneca. Received honoraria from Targeted Oncology, SITC. All other authors declare no conflicts of interest associated with the present study., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Imparting knowledge in the operating room represents a particular challenge in student teaching., Objective: Participation in the operating room was compared with teaching via a surgical video course as part of the block practical course in ophthalmology at the University of Lübeck., Methods: All students took part in both observation in the operating room and in the video course. Thereafter, they were surveyed on both forms of teaching using the same items taken from a catalogue of questions. Based on the evaluation of these answers, we carried out a direct comparison between participation in the operating room and teaching with surgical videos., Results: Teaching of the surgical content and steps (p < 001), the underlying clinical picture (p < 001), the surgical indication (p < 001), and the surgical outcome (p < 001) was rated better in the surgical video course than for participation in the operating room. The assessment of learning gain (p < 001) was also higher in the surgical video course. Only the interest in ophthalmic surgery (p = 0.62) was rated similarly between participation in the operating room and teaching with surgical videos., Conclusion: The video format is well suited for pure knowledge transfer. However, it does not replace participation in the operating room, where not only the operation itself can be followed but also the preparation and post-processing of the surgery. We therefore prefer a combination of both parts of the course and will retain the structure presented. In addition, we will use the knowledge gained to further improve teaching in the operating room., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: S. Gniesmer, S.R. Sonntag, S. Grisanti, V.E. Pawlik, R. Piria, M. Prasuhn, S. Grisanti und A. Mohi geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s).)

Introduction: During the recent INTERACTION group congress held on February 16-17, 2024, in Milan, Italy, many aspects of early-stage lung cancer treatment were explored. This review delves into perioperative treatment, a rapidly evolving field with an expanding therapeutic arsenal that includes chemotherapy, target therapy, and immunotherapy. The challenge remains in tailoring treatment strategies to individual patients, identifying patients best suited for surgery versus those necessitating trimodal treatment, particularly in distinguishing surgical candidates from those requiring multimodal approaches and not suitable for surgical approach., Materials and Methods: We conducted a literature review of phase III trials on immunotherapy and target therapy in early-stage non-small cell lung cancer (NSCLC), searching in MEDLINE, EMBASE and LILACS, adding the latest data from the European Society of Medical Oncology (ESMO) 2023 and 2024, American Society of Clinical Oncology (ASCO) 2024, and the World Conference on Lung Cancer (WCLC) 2024 conferences. A guidance on unresolved and controversial issues from the panel has been reported, also highlighting the remaining limitations that warrant further investigation and refinement in this field., Results: Most recent data on early-stage NSCLC have been critically reviewed. The panel emphasized the importance of distinguishing, from the outset in a multidisciplinary setting, patients who are suitable for surgical treatment from those who are not. In this context, the importance of accurate staging at the time of diagnosis was highlighted. A paradigm shifts regarding the timing of molecular NGS DNA and RNA testing is strongly recommended., Conclusion: Decisions regarding perioperative treatment in early-stage lung cancer demand early consideration, involving a multidisciplinary team and require an upfront NGS analysis. Such an approach ensures personalized care aligned with each patient's unique characteristics, optimizing treatment efficacy and overall well-being., Competing Interests: Declaration of Competing Interest None., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objectives : Accurate target definition, treatment planning and delivery increases local tumor control for radiotherapy by minimizing collateral damage. To achieve this goal for uveal melanoma (UM), tantalum fiducial markers (TFMs) were previously introduced in proton and photon beam radiotherapy. However, TFMs cause pronounced scattering effects in imaging that make the delineation of small tumors difficult. The aim of this study was to evaluate silicone fiducial markers (SFMs) for the guiding of stereotactic radiosurgery (SRS) for UM. Methods : In this retrospective interventional pilot case series, three patients with small UMs 3 mm or less in tumor thickness and ≤10 mm in largest basal diameter received silicone fiducial markers. The fiducial markers were punched out (3 mm) from conventional silicone encircling bands for buckle surgery. The markers were sutured onto the sclera at the tumor margins according to the use of TFMs. MRI and CT images were used for the localization of the tumor and the markers before robotic-guided SRS. Results : The silicone fiducial markers were punched out easily from the original band, better to handle than TFMs and easy to suture onto the sclera. They could be visualized in both MRI and CT, but were more visible in CT. In the absence of scattering effects, both the markers and thus the tumor boundaries could be clearly delineated. Conclusions : This is the first report that introduces fiducial markers intraoperatively shaped from conventional silicone encircling bands usually used for retinal detachment surgery. The SFMs allow more accurate tumor delineation, resulting in the more precise planning and administration of SRS when compared to TFMs. This simple modification has a major impact on a well-known treatment approach.

Background: Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder presenting with cerebellar ataxia, sensory-motor axonal neuropathy, oculomotor apraxia, cerebellar atrophy and high alpha-fetoprotein (AFP) serum level. AOA2 is due to coding mutations of the SETX gene, mapped to chromosome 9q34. Seldom noncoding mutations affecting RNA processing have been reported too. To date psychiatric symptoms have never been reported in AOA2., Case Presentation: A 19 years-old man came to our attention for progressive gait ataxia debuted five years earlier. His past medical history was unremarkable, while his parents were consanguineous. On neurological examination, he had bilateral horizontal gaze-evoked nystagmus with hypometric saccades and saccadic horizontal smooth pursuit, appendicular ataxia, limbs and trunk myoclonic involuntary movements with hands' dystonic postures and dance of the tendons. Psychological evaluation described intrusive and obsessive thoughts experienced by the patient, then diagnosed as obsessive-compulsive disorder. Blood tests detected an elevated AFP level. Brain MRI showed cerebellar atrophy, while electroneuromyography revealed an axonal sensory-motor polyneuropathy. In the suspicion of a pathology belonging to the autosomal recessive cerebellar ataxias (ARCA) spectrum disorder, a direct search of point mutations by whole-exome sequencing was performed revealing a novel biallelic variant in SETX gene (c.6208+2dupT), which was classified as likely pathogenic., Conclusion: The present case expands the genotypic and phenotypic spectrum of AOA2, reporting a novel likely pathogenic SETX mutation (c.6208+2dupT) and highlighting an early psychiatric involvement in AOA2, suggesting the need for psychiatric assessment in these neurologic patients., Competing Interests: Declaration. Ethical statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent has been obtained from the patient. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines, (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Microinvasive procedures have become established in glaucoma surgery and are preferred for patients with target pressure values that are not too low. Excimer laser trabeculotomy (ELT) represents such a minimally invasive approach and can easily be combined with cataract surgery., Objective: Over 12 months the reduction in intraocular pressure (IOP), the number of antiglaucoma drugs and the incidence of adverse events were evaluated using the new Elios TM method (Elios Vision GmbH, Germering, Germany) for real-life data from a heterogeneous patient population undergoing ELT in combination with cataract surgery (phaco-ELT)., Material and Methods: In this study 20 eyes of 13 patients who underwent phaco-ELT were retrospectively analyzed. After standard phacoemulsification with posterior chamber lens implantation, 10 microchannels were created using the excimer laser. The patients were followed for 12 months and the intraocular pressure (IOP), number of antiglaucoma drugs and the occurrence of adverse events were analyzed., Results: The average age was 65 years. The preoperative IOP was 17.5 (± 5.3) mm Hg. The mean IOP reduction was 4.8 mm Hg (27.4%, p < 0.001) on the first postoperative day, 3.2 mm Hg (18.3%, p = 0.22) after 6 months and 2.5 mm Hg (14.3%, p = 0.14) at 12 months. The number of antiglaucoma drugs decreased from an average of 3.2 (± 1.3) preoperatively to 0.5 (± 0.9) on day 1 (p < 0.001), 1.9 (± 1.2) after 6 months (p = 0.008) and 2.2 (± 1.3) after 12 months (p = 0.013)., Discussion: In our cohort ELT in combination with cataract surgery is a safe minimally invasive procedure leading to an IOP reduction of 14.3% and a reduction of pressure-lowering medication by 1 active ingredient in patients with low initial pressure at 1‑year follow-up. As no implant is used in ELT and the conjunctiva remains untouched, subsequent procedures, including bleb-related surgery, are not negatively affected., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: S. Grisanti ist Beraterin für Elios vision, Glaukos und iStar Medical. S. Gniesmer und S.R. Sonntag geben an, dass kein Interessenkonflikt besteht. Alle beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethikkommission durchgeführt., (© 2024. The Author(s).)