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Palmar fasciitis and polyarthritis syndrome ( PFPAS) is an uncommon disorder characterized by diffuse inflammation of the palmar fascia, tendon sheaths, and joints of the fingers and wrists, which rapidly progresses to flexion contracture of the hands. This paraneoplastic syndrome, originally linked to ovarian carcinoma, has also been associated with multiple different malignancies. As PFPAS usually precedes the detection of cancer, its symptoms should raise the suspicion of an underlying malignancy and should be thoroughly investigated. [ABSTRACT FROM AUTHOR]

Patients with metastatic urothelial carcinoma (mUC) are typically elderly and often have other comorbidities that require the use of concomitant medications. In our study we evaluated the association of concomitant use of antibiotics (ATBs), proton pump inhibitors (PPIs), corticosteroids, statins, metformin and insulin with patient outcomes and we validated the prognostic role of a concomitant drug score in mUC patients treated with enfortumab vedotin (EV) monotherapy. Data from 436 patients enrolled in the ARON-2 EV retrospective study were analyzed according to the concomitant medications used at baseline. Finally, the patients were stratified into three risk groups according to the concomitant drug score based on ATBs, corticosteroids and PPIs. Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models. Inferior survival outcomes were observed in ATB users compared to non-users (OS: 7.3 months, 95%CI 5.0 - 12.3 vs 13.7 months, 95%CI 12.2 - 47.3, p = 0.001; PFS: 5.1 months 95%CI 3.3 - 17.7 vs 8.3 months, 95%CI 7.1 - 47.3, p = 0.001) and also in corticosteroid users compared to non-users (OS: 8.4 months, 95%CI 6.6 - 10.0 vs 14.2 months, 95%CI 12.7 - 47.3, p < 0.001; PFS: 6.0 months 95%CI 4.6 - 7.9 vs 8.9 months, 95%CI 7.2 - 47.3, p = 0.004). In the Cox multivariate analysis, the concomitant drug score was a significant factor predicting both OS (HR = 1.32 [95% CI 1.03 - 1.68], p = 0.026) and PFS (HR = 1.23 [95% CI 1.01 - 1.51], p = 0.044). Our findings suggest detrimental impact of concomitant use of ATBs and corticosteroids on survival outcomes and the prognostic utility of the concomitant drug score in previously treated mUC patients receiving EV., Competing Interests: Declarations. Conflict of interest: Ondrej Fiala received honoraria from Roche, Janssen, GSK and Pfizer for consultations and lectures unrelated to this project. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, Astellas. All unrelated to the present paper. Alfonso Gómez de Liaño has received honoraria for advisory boards, consultation, or educational events from AAA HealthCare, Astellas, AstraZeneca, Bayer, BMS, Ipsen, Johnson & Johnson, MSD, Merck KGaA, Novartis, Recordati Rare Diseases and Roche (all unrelated to the present paper); and has Institutional research funding from AstraZeneca, Genmab A/S, Gilead Sciences, Johnson & Johnson, Merck KGaA, MSD, Roche and Syneos Health. Takahiro Kimura is a paid consultant/advisor of Astellas, AstraZeneca, Bayer, Janssen, Sanofi, and Takeda. Martin Angel received honoraria from Roche, Johnson & Johnson, Raffo and Pfizer for consultations and lectures unrelated to this project. Javier Molina-Cerrillo: reports research funding from Roche, Ipsen, Pfizer, and Janssen; travel support from Pfizer, Janssen, Ipsen, and BMS; a consulting or advisory role with Ipsen, Roche, BMS, Pfizer, Sanofi, Janssen, Astellas, Eisai, Adium and MSD. All unrelated to the present paper. Maria T Bourlon is a consultant of Bristol Myers Squibb, Merck, MSD, Gilead, Astellas and Asofarma and a speaker for Janssen Pharmaceuticasl, MSD, Merck, and Astellas. All unrelated to the present paper. Andrey Soares: Honoraria from Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, Adium. Consulting or Advisory Role from Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen, Pfizer, Novartis. Research Funding from Bristol-Myers Squibb (Inst), Astellas (Inst), AstraZeneca (Inst). Travel, Accommodations, Expenses from Bayer, Janssen, Ipsen, Adium, MSD, Merck Serono. Ownership: BIO, Brazilian Information Oncology. All are unrelated to this study. Nonfinancial with no other potential conflicts of interest were reported. Yüksel Ürün has served on advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen ilaç, Gilead, GSK, Janssen, Merck, MSD, Novartis, Pfizer, Roche and received travel grants, honoraria or consultation fees from Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen İlaç, Gilead, GSK, Janssen, Merck, Novartis, Pfizer and Roche. All unrelated to the present paper. Bohuslav Melichar has received honoraria from Roche, BMS, MSD, Novartis, Merck Serono, Eli Lilly, Pfizer, and AstraZeneca, all unrelated to the present paper. Alexandr Poprach has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer, unrelated to this project. Vincenza Conteduca has served as a consultant/advisory board member for Johnson&Johnson, Astellas, Merck, AstraZeneca, Amgen, EISAI, Recordati, Novartis, and Bayer and has received speaker honoraria or travel support from Astellas, Johnson&Johnson, Ipsen, Bayer, Gilead, and BristolMyers Squibb. Fernando Sabino M. Monteiro: Research support was provided by Merck Sharp Dome. Honoraria from Janssen, Ipsen, Bristol Myers Squibb, and Merck Sharp Dome. Ownership: BIO, Brazilian Information Oncology. All are unrelated to this study. Tomas Buchler has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Bristol Myers Squibb, Ipsen, Roche, Astellas, Merck, Eisai, Merck Sharp Dohme, Novartis, AstraZeneca, Janssen, and Pfizer, all unrelated to this project. Francesco Massari has received research support and/or honoraria from Advanced Accelerator Applications, Astellas, Astra Zeneca, Bayer, BMS, Janssen, Ipsen, MSD, Pfizer outside the submitted work. Javier Molina-Cerrillo declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen, and BMS. JMC has received research grants from Pfizer, IPSEN and Roche. Shilpa Gupta is a consultant for Bristol Myers Squibb, Merck, Pfizer, Gilead, Bayer, Seattle Genetics, is speaker for Bristol Myers Squibb and has Institutional research funding from Seatte Genetics, Pfizer, Merck, Bristol Myers Squibb, Roche, Novartis, Tyra Biosciences. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas and Bayer, all unrelated to the present paper. Other authors declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Ethical approval: The study protocol was approved on September 28, 2023, by the Ethical Committee of the coordinating center (Marche Region-Italy-No. 2022 39/7875, Study Protocol “ARON 2 Study” NCT05290038) and by the Institutional Review Boards of participating centers. Consent to participate: The Informed consent with subsequent analysis of the follow-up data was obtained from all participants. Consent for publication: All authors have approved the manuscript for publication., (© 2025. The Author(s).)

Vascular malformations, which result from anomalies in angiogenesis, include capillary, lymphatic, venous, arteriovenous, and mixed malformations and affect specific vessel types. Historically, treatments such as sclerotherapy and surgery have shown limited efficacy in complicated cases. Most vascular malformations occur sporadically, but some can be inherited. They result from mutations similar to oncogenic alterations, activating pathways such as PI3K-AKT-mTOR or Ras-MAPK-ERK. Recognizing these parallels, we highlight the potential of targeted molecular inhibitors, repurposing anticancer drugs for the treatment of vascular malformations. This case-based review explores recent developments in precision medicine for slow-flow and fast-flow vascular malformation., (Copyright © 2024 by The American Society of Hematology.)

Competing Interests: Declarations. Ethics approval: Ethics approval has been obtained by the local IRB. Consent to participate: Not applicable. Consent to publish: The authors affirm that the patient provided informed consent for publication of the images. Competing interests: The authors declare they have no competing neither financial interests.

Background/Objectives: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that combines monomethyl auristatin E (MMAE), a potent cytotoxic agent, with a monoclonal antibody targeting Nectin-4. It has emerged as a promising therapy for metastatic urothelial carcinoma (mUC), either as monotherapy or in combination with pembrolizumab, improving significantly the overall survival of these patients. EV is associated with common adverse events, including skin reactions, glucose imbalance, and peripheral neuropathy, which are usually mild in severity and easily manageable. Methods: Following an initial case of pleuro-pneumopathy occurring in a patient treated with EV, we conducted a retrospective analysis of EV effects on pulmonary imaging. Results: In a cohort of 20 all-comers mUC patients, we identified three cases of potentially EV-related lung toxicity, resulting in a pleuro-pneumopathy rate of 15%. Two of these cases appeared highly symptomatic and required high steroid doses, with a rapid resolution of symptoms and normalization of radiological findings. In one patient, rechallenge of EV was associated with reoccurrence of pneumopathy. We described the clinical and radiological features of these cases, as well as their evolution after EV discontinuation and rechallenge. Conclusions: This case series underscores the importance of close pulmonary monitoring during EV treatment.

Background: Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, "primary refractory" (P ref ), face dismal outcomes., Objective: Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of P ref patients., Methods: This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan-Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve., Results: In our study, the P ref rate was 19%. Nivolumab/ipilimumab showed the highest P ref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-P ref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for P ref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of P ref . This study presents limitations, mainly because of its retrospective design., Conclusions: The ARON-1 study provides valuable insights into P ref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches., Competing Interests: Declarations Funding No external funding was used in the preparation of this article. Conflicts of Interest/Compting Interests Ondrej Fiala received honoraria from Novartis, Janssen, Merck, BMS, MSD, Pierre Fabre, and Pfizer for consultations and lectures unrelated to this project. Sebastiano Buti has received honoraria for speaking at scientific events and advisory roles from Astra Zeneca, BMS, Ipsen, Merck, Eisai, MSD, Novartis, and Pfizer and research funding from Novartis and Pfizer unrelated to this project. He has also been on the advisory board for Gentili. Francesco Massari has received research support and/or honoraria from Astellas, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. Enrique Grande has received honoraria for speaker engagements and advisory roles or received funding for continuous medical education from Adacap, Amgen, Angelini, Astellas, Astra Zeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis-Oncology, Eisai, Eusa Pharma, Genetracer, Guardant Health, HRA-Pharma, Ipsen, ITM-Radiopharma, Janssen, Lexicon, Lilly, Merck KGaA, MSD, Nanostring Technologies, Natera, Novartis, ONCODNA (Biosequence), Palex, Pharmamar, Pierre Fabre, Pfizer, Roche, Sanofi-Genzyme, Servier, Taiho, and Thermo Fisher Scientific and research grants from Pfizer, Astra Zeneca, Astellas, and Lexicon Pharmaceuticals. All of the above are unrelated to the present paper. Alexandr Poprach has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer, unrelated to this project. Javier Molina-Cerrillo declares consultant, advisory, or speaker roles for Ipsen, Roche, Pfizer, Sanofi, Janssen, and BMS unrelated to this project. Zin W. Myint has received research support from Merck unrelated to the present paper. Ray Manneh Kopp has received research support and/or honoraria from Amgen, Astellas, Astra Zeneca, Bayer, BMS, Eli Lilly, Janssen, MSD, Pfizer, Tecnofarma and Roche, unrelated to this project. Jakub Kucharz has received honoraria from Angelini, Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, IPSEN, Janssen, Merck MSD, Novartis, and Pfizer, and research funding from Novartis, all unrelated to the present paper. Fernando Sabino M. Monteiro has received research support from Janssen and Merck Sharp Dome and honoraria from Janssen, Ipsen, Bristol Myers Squibb, and Merck Sharp Dome, all unrelated to the present paper. Ravindran Kanesvaran has received fees for speaker bureau and advisory board activities from the following companies; Pfizer, MSD, BMS, Eisai, Ipsen, Johnson and Johnson, Merck, Amgen, Astellas, and Bayer, unrelated to this project. Tomáš Büchler has received research support from AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Merck KGaA, MSD, and Novartis; consulting fees from Bristol Myers Squibb, Astellas, Janssen, and Sanofi/Aventis; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Ipsen, Bristol Myers Squibb, AstraZeneca, Roche, Servier, Accord, MSD, and Pfizer, all unrelated to the present paper. Andrey Soares has received honoraria from Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, Adium. Consulting or Advisory Role from Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen, and Pfizer, research Funding from Bristol-Myers Squibb (Inst), Astellas (Inst), and AstraZeneca (Inst), travel, accommodations, and expenses from Bayer, Janssen, Ipsen, Adium, MSD, and Merck Serono, and ownership in BIO, Brazilian Information Oncology. All are unrelated to this study. Camillo Porta has received honoraria from Angelini Pharma, AstraZeneca, BMS, Eisai, Exelixis, Genenta, Ipsen, Merck Serono, and MSD and acted as a Protocol Steering Committee Member for Eisai and MSD, unrelated to this project. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, A.A.A. and Bayer, all unrelated to the present paper. Daniele Santini, Haoran Li, Giandomenico Roviello, Se Hoon Park, Umberto Basso, Martina Catalano, Emmanuel Seront, Jawaher Ansari, Marwan Ghosn, Fabio Calabrò, Dipen Bhuva, Maria T. Bourlon, Michela Roberto, Mattia Alberto Di Civita, Veronica Mollica, Andrea Marchetti, Nicola Battelli, Marco Ricci, and Aristotelis Bamias have no conflicts of interest that are directly relevant to the content of this article. Tomas Buchler and Camillo Porta are Editorial Board members of Targeted Oncology. Tomas Buchler and Camillo Porta were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethics Approval The “ARON-1” project obtained approved from the Ethics Committee of the Marche Region (2021-492) and adhered to the principles outlined in the Declaration of Helsinki. Consent to Participate Informed consent was obtained from all individual participants included in the study. Consent for Publication Not applicable. Availability of Data and Material The datasets generated during and/or analyzed in the current study are available from the corresponding author on reasonable request. Code Availability Not applicable. Authors’ Contributions Conception and design: DS, MS, FM; acquisition of data: DS, MS, FM; analysis and interpretation of data: DS, MS, FM; drafting of the manuscript: DS, MS, FM; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: MS; supervision: MS, FM., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Enfortumab vedotin (EV) has been approved for the treatment of patients with locally advanced/metastatic urothelial carcinoma (la/mUC) who previously received platinum-based chemotherapy followed by immune checkpoint inhibitors. However, the pivotal clinical trials did not include patients previously treated with avelumab maintenance therapy., Objective: The aim of the present retrospective analysis was to assess the effectiveness of EV following avelumab in patients with mUC enrolled in the ARON-2 EV study., Patients and Methods: The study included 182 patients with mUC treated with EV following avelumab maintenance. The primary objective was to assess clinical outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and duration of response (DoR). Statistical analysis involved Fisher exact test, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models., Results: Median OS and PFS were 12.7 (95% CI 10.2-14.1) and 7.9 (95% CI 6.4-9.9) months, respectively. Complete response (CR) was achieved in 5% and partial response (PR) in 34% of patients, with an ORR of 39%. The DoR in patients who achieved CR/PR was 10.9 months (95% CI 8.1-11.4). The incidence of grade ≥ 3 peripheral neuropathy and skin rash was 9%, followed by 8% of grade ≥ 3 diarrhea and 4% of grade ≥ 3 hyperglycemia., Conclusions: The results of our large international retrospective study confirm the effectiveness of EV and endorse its use in the population of patients with mUC treated with EV following the frontline platinum-based chemotherapy and subsequent maintenance treatment with avelumab., Competing Interests: Declarations Funding No external funding was used in the preparation of this manuscript. Conflicts of Interest Ondřej Fiala received honoraria from Roche, Janssen, GSK, and Pfizer for consultations and lectures unrelated to this project. Francesco Massari has received research support and/or honoraria from Advanced Accelerator Applications, Astellas, Astra Zeneca, Bayer, BMS, Janssen, Ipsen, MSD, and Pfizer outside the submitted work. Umberto Basso received honoraria for Bristol-Myers Squibb, Novartis, and Astra Zeneca; research funding from Ipsen; and travel grants from Bristol-Myers Squibb, Janssen Oncology, Astellas Pharma, MSD Oncology, Merck/Pfizer, and Bayer, all unrelated to this project. Sebastiano Buti received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, and Astellas, all unrelated to the present paper. Yüksel Ürün has served on advisory board for Abdi-İbrahim, Astellas, AstraZeneca, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen ilaç, Gilead, GSK, Janssen, Merck, MSD, Novartis, Pfizer, and Roche and received travel grants, honoraria, or consultation fees from Abdi-İbrahim, Astellas, Bristol Myers-Squibb, Deva, Eczacıbaşı, Gen İlaç, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, and Roche, all unrelated to the present paper. Maria T. Bourlon is a consultant of Bristol Myers Squibb, Merck, MSD, Gilead, Astellas, and Asofarma and a speaker for Janssen Pharmaceuticasl, MSD, Merck, and Astellas, all unrelated to the present paper. Mimma Rizzo has received honoraria as a speaker/consultant by MSD, Merck Serono, Astrazeneca, Bristol Myers Squibb, Eisai, and Gilead, all unrelated to the present paper. Linda Cerbone has received honoraria for advisory boards, speaker engagements, and scientific consultancy for educational purposes from AstraZeneca, EISAI, MSD, Ipsen, BMS, and A.A.A.; and is a past MSD employee in Medical Affairs. Javier Molina-Cerrillo reports research funding from Roche, Ipsen, Pfizer, and Janssen; travel support from Pfizer, Janssen, Ipsen, and BMS; and a consulting or advisory role with Ipsen, Roche, BMS, Pfizer, Sanofi, Janssen, Astellas, Eisai, Adium, and MSD, all unrelated to the present paper. Álvaro Pinto is a member of advisory boards of Pfizer, Novartis, Ipsen, BMS, Janssen, Astellas, Sanofi, Bayer, Clovis, Roche, MSD, Pierre Fabre, and Merck; has received research support from Pfizer and BMS; clinical trial payments from Pfizer, Bayer, Janssen, MSD, Clovis, Pharmacyclics, BMS, Sanofi, Astra Zeneca, Roche, Eisai, and Aveo; and travel arrangements from Janssen, Roche, Pfizer, BMS, and Ipsen, all unrelated to the present paper. Andrey Soares reports honoraria from Janssen, Pfizer, Bayer, AstraZeneca, Astellas Pharma, Merck Serono, Sanofi, Ipsen, and Adium; consulting or advisory role from Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol-Myers Squibb, Adium, Ipsen, Pfizer, and Novartis; research funding from Bristol-Myers Squibb (Inst), Astellas (Inst), and AstraZeneca (Inst); travel, accommodations, and expenses from Bayer, Janssen, Ipsen, Adium, MSD, and Merck Serono; and ownership in BIO, Brazilian Information Oncology; all unrelated to this study. Alexandr Poprach has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from BMS, Ipsen, Roche, Astellas, Merck, Eisai, MSD, Novartis, and Pfizer, unrelated to this project. Gian Paolo Spinelli has received payment or honoraria for advidory boards from Novartis, Roche, and Bayer, unrelated to this project. Martin Angel received honoraria from Roche, Johnson & Johnson, Raffo, and Pfizer for consultations and lectures unrelated to this project. Fernando Sabino M. Monteiro reports research support provided by Merck Sharp Dome; honoraria from Janssen, Ipsen, Bristol Myers Squibb, and Merck Sharp Dome; and ownership in BIO, Brazilian Information Oncology, all unrelated to this study. Camillo Porta acted as a remunerated consultant and/or speaker for Angelini Pharma, AstraZeneca, BMC, Eisai, Exilixis, Genenta, Ipsen, Merck Serono, and MSD; as a protocol steering committee member for Eisai and MSD; and as an Independent Review Board member for Genenta. Shilpa Gupta is a consultant for Bristol Myers Squibb, Merck, Pfizer, Gilead, Bayer, and Seattle Genetics; is a speaker for Bristol Myers Squibb; and has institutional research funding from Seatte Genetics, Pfizer, Merck, Bristol Myers Squibb, Roche, Novartis, and Tyra Biosciences. Matteo Santoni has received research support and honoraria from Janssen, Bristol Myers Squibb, Ipsen, MSD, Astellas, and Bayer, all unrelated to the present paper. Patrizia Giannatempo, Enrique Grande, Zin W. Myint, Ugo De Giorgi, Renate Pichler, Francesco Grillone, Fabio Calabrò, Luca Galli, Ravindran Kanesvaran, Giandomenico Roviello, Jakub Kucharz, Se Hoon Park, Emmanuel Seront, Carlo Messina, Daniele Santini, Akihiro Yano, Lorena Incorvaia, Martina Catalano, Luigi Formisano, Gaetano Facchini, Giuseppe Fornarini, Sara Elena Rebuzzi, Cecilia Nasso, Marco Stellato, Deniz Tural, Gaetano Aurilio, Ilana Epstein, Francesco Carrozza, Giovanni Benedetti, Tomáš Büchler, Cinzia Ortega, Roubini Zakopoulou, Nicola Battelli, and Joaquin Bellmunt declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Tomáš Büchler and Camillo Porta are Editorial Board members of Targeted Oncology. Tomáš Büchler and Camillo Porta were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethics Approval The study protocol was approved on 28 September 2023, by the Ethical Committee of the coordinating center (Marche Region – Italy – no. 2022 39/7875, Study Protocol “ARON 2 Study” NCT05290038) and by the Institutional Review Boards of participating centers. Consent to Participate Informed consent with subsequent analysis of the follow-up data was obtained from all participants. Consent for Publication Not applicable. Availability of Data and Material The datasets generated and/or analyzed during the current study are not publicly available due to patient data security but are available from the corresponding author on reasonable request. Code Availability Not applicable. Author Contributions Study concept and design: all authors; acquisition of data: all authors; analysis and interpretation of data: all authors; drafting of the manuscript: Fiala, Massari, Gupta, and Santoni; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: Santoni; obtaining funding: none; administrative, technical, or material support: none; and supervision: Gupta and Santoni., (© 2024. The Author(s).)

Vascular malformations, which arise from anomalies in angiogenesis, encompass capillary, lymphatic, venous, arteriovenous, and mixed malformations, each affecting specific vessel types. Historically, therapeutic options such as sclerotherapy and surgery have shown limited efficacy in complicated malformations. Most vascular malformations stem from hereditary or somatic mutations akin to oncogenic alterations, activating the PI3K-AKT-mTOR, RAS-MAPK-ERK, and G-protein coupled receptor pathways. Recognizing the parallels with oncogenic mutations, we emphasize the potential of targeted molecular inhibitors in the treatment of vascular malformations by repurposing anticancer drugs. This review delves into the recent development and future use of such agents for the management of slow- and fast-flow vascular malformations, including in more specific situations, such as prenatal treatment and the management of associated coagulopathies., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC., Methods: We performed a multicenter retrospective analysis of real-world data collected for patients with advanced pRCC treated in 40 centers in 12 countries as part of the ARON-1 project (NCT05287464). The primary endpoints were overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and time to second progression (PFS2). OS, PFS, and PFS2 were estimated using the Kaplan-Meier method and results were compared between the treatment groups using a log-rank test. Univariate and multivariable analyses were carried out using Cox proportional-hazard models., Key Findings and Limitations: We included 200 patients with metastatic pRCC, of whom 73 were treated with IO-based combinations and 127 with TKIs. Median OS was 22.5 mo in the TKI group 28.8 mo in the IO group (p = 0.081). Median PFS was 6.4 mo in the TKI group and 17.4 mo in the IO group (p < 0.001). The ORR was higher in the IO group than in the TKI group (41% vs 27%; p = 0.037)., Conclusions and Clinical Implications: Our results show that IO-based combinations have superior efficacy outcomes to TKIs for first-line treatment of metastatic pRCC., Patient Summary: The ARON-1 project collects clinical data for patients with kidney cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic kidney cancer of a specific subtype to evaluate the efficacy of different first-line treatments. Patients treated with immune-based combinations had better outcomes than patients treated with tyrosine kinase inhibitors., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)