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Introduction: Graft optimization is a necessity in order to develop uterus transplantation from brain-dead donors, as a complement to living donors, as these grafts are rare and the last organs retrieved in multiple organ donation. The aim of this study was to assess the feasibility and interest of hypothermic machine perfusion (HMP) in uterus transplantation using a porcine model; secondary outcomes were the evaluation of the graft's tolerance to a prolonged cold ischaemia time and to find new biomarkers of uterus viability., Material and Methods: Fifteen uterus allotransplantations were performed in a porcine model, after 18 h of cold ischaemia, divided in three groups: Static cold storage in a HTK solution, HMP (with the VitaSmart (™) machine Bridge to Life Ltd.) with a UW-MP solution, and static cold storage in a UW solution. The main outcome was macroscopic: uterine arteries pulsatility, recoloration, and bleeding at the cut. Secondary outcomes were histological analyses (Zitkute and inflammation scores), caspase3 immunohistochemistry and plasmatic dosage of biomarkers., Results: 14/15 allotransplantations were performed according to the protocol and met the criteria of macroscopic vitality. Grafts treated with HMP (MP did not show significantly more tissue) damage than the recipient's uterus, contrary to grafts in static cold storage, independently of the solution used. This difference disappeared one and 3 h after uterus transplantation. Plasma dosages before and after uterus transplantation did not allow to identify a new biomarker of uterus viability., Conclusions: HMP is feasible in a porcine model, without inflicting damage on the grafts during cold ischaemia time. Grafts exposed to HMP seemed to better endure reperfusion phenomena, but this advantage did not last over time., (© 2025 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Neuroblastoma is a common childhood tumor originating from neural crest progenitors with variable clinical behavior. Despite improved overall survival, factors such as stage, histoprognosis, MYCN status, and age still influence outcome. MCM6 regulates DNA replication and contributes to cancer progression. PRAME, first identified in melanoma, also acts on cell replication, epithelial-mesenchymal transition, and cell migration and has been associated with poor outcomes in several cancers, including neuroblastoma, using molecular biology techniques. The study aims to investigate MCM6 and PRAME expression and prognostic roles in neuroblastoma. A retrospective study was conducted, which included data of 84 patients with neuroblastoma diagnosed between 2000 and 2022, sourced from the pediatric tumor registry. Patient's characteristics and prognostic tumor factors were collected. Expression of MCM6 and PRAME proteins was evaluated using digital image analysis techniques. Univariate and multivariate analyses were performed using Cox regression to assess the impact of protein expression on survival and their associations with these prognostic factors. A total of 84 children diagnosed with neuroblastoma were included. MCM6 and PRAME were associated with unfavorable histologies (p = 0.03). PRAME was associated with bone marrow metastases (p < 0.01), high mitotic-karyorrhectic index (p = 0.04), and poor histoprognosis (p < 0.01). PRAME and MCM6 expression was correlated with several neuroblastoma prognostic factors. PRAME was significantly (p = 0.05) associated with poor event-free survival (EFS) and not significantly (p = 0.08) associated with overall survival (OS). Although statistical significance was not reached in multivariate analysis, the trends strongly suggested that the overexpression of MCM6 and PRAME was correlated with decreased survival., Competing Interests: Declaration of competing interest The authors declare that they have no financial or intellectual conflicts of interest pertaining to the contents of this manuscript., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The 2030 French Innovation Healthcare national plan defined "Digital Healthcare" as one of its priority. The deployment of digital pathology and artificial intelligence fits perfectly into this framework. Therefore we evaluated the pathologist's interest in those fields by conducting an online survey among members of the French Society of Pathology, mainly composed of senior pathologists and trainees (n=2301). We collected 123 answers originating nationwide and representative of all status of practice. A heavy majority of participants (83%) declared themselves "interested or very interested" in digital transition and AI. Twenty-six percent of participants took part in academic research projects and 20% in industrial research projects. With digital pathology becoming increasingly common nationwide, there is a growing interest of pathologists in the development and validation of AI algorithms. In order to support this dynamic, a commission for research on artificial intelligence has been created under the authority of the French Society of Pathology., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: To update the French recommendations for the management of kidney cancer., Methods: A systematic review of the literature was conducted for the period from 2014 to 2024. The most relevant articles concerning the diagnosis, classification, surgical treatment, medical treatment, and follow-up of kidney cancer were selected and incorporated into the recommendations. The recommendations have been updated specifying the level of evidence (strong or weak)., Results: Kidney cancer following prolonged occupational exposure to trichloroethylene should be considered an occupational disease. The reference examination for the diagnosis and staging of kidney cancer is the contrast-enhanced thoraco-abdominal CT scan. PET scans are not indicated in the staging of kidney cancer. Percutaneous biopsy is recommended in situations where its results will influence therapeutic decisions. It should be used to reduce the number of surgeries for benign tumors, particularly avoiding unnecessary radical nephrectomies. Kidney tumors should be classified according to the pTNM 2017 classification, the WHO 2022 classification, and the ISUP nucleolar grade. Metastatic kidney cancers should be classified according to IMDC criteria. Surveillance of tumors smaller than 2cm should be prioritized and can be offered regardless of patient age. Robot-assisted laparoscopic partial nephrectomy is the reference surgical treatment for T1 tumors. Ablative therapies and surveillance are options for elderly patients with comorbidities for tumors larger than 2cm. Stereotactic radiotherapy is an option to discuss for treating localized kidney tumors in patients not eligible for other treatments. Radical nephrectomy is the first-line treatment for locally advanced localized cancers. Pembrolizumab is recommended for patients at high risk of recurrence after surgery for localized kidney cancer. In metastatic patients, cytoreductive nephrectomy can be immediate in cases of good prognosis, delayed in cases of intermediate or poor prognosis for patients stabilized by medical treatment, or as "consolidation" in patients with complete or major partial response at metastatic sites after systemic treatment. Surgical or local treatment of metastases can be proposed for single lesions or oligometastases. Recommended first-line drugs for metastatic clear cell renal carcinoma are combinations of axitinib/pembrolizumab, nivolumab/ipilimumab, nivolumab/cabozantinib, and lenvatinib/pembrolizumab. Patients with non-clear cell metastatic kidney cancer should be presented to the CARARE Network and prioritized for inclusion in clinical trials., Conclusion: These updated recommendations are a reference that will enable French and French-speaking practitioners to optimize their management of kidney cancer., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Renal cell carcinomas (RCC) represent a group of heterogeneous tumors whose classification has greatly evolved since 1981. The latest update in 2022 classifies all renal cell carcinomas into six categories according to their morphology or the detection of specific molecular alterations. Molecular disassembly of renal cell carcinomas with papillary features has enabled the identification of new entities characterized by a specific molecular alteration, such as Fumarate Hydratase (FH) deficient RCC, TFE3-rearranged RCC or TFEB-altered RCC. This new classification allows for a more accurate diagnosis but requires a thorough knowledge of the genomic alterations to search for with immunohistochemical or molecular biology techniques. According to the new WHO 2022 classification, papillary renal cell carcinoma (PRC) type 1 or type 2 classification is no longer recommended. A classification based on nucleolar ISUP grade must be preferred: low-grade PRC (ISUP 1-2) or high-grade PRC (ISUP 3-4). The other prognostic factors remain the same: the pTNM stage, lymphovascular invasion, and the presence or absence of dedifferentiated areas referring to sarcomatoid or rhabdoid features. Of note, the presence of necrosis is not currently recognized as a poor prognostic element for this type of carcinoma. The diagnosis of high-grade PRC is from now on a diagnosis of exclusion. It can only be sustained after having ruled out TFE3-rearranged RCC, TFEB-altered RCC, and FH-deficient RCC. For clinicians, the diagnosis of PRC implies suggesting an oncogenetic consultation to screen for an associated genetic tumor syndrome regardless of the patient's age., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: Papillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets., Methods: The expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 68 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort. Our primary endpoint was to estimate the prevalence of PD-L1 expression and its prognostic impact in metastatic pRCC. Secondary endpoints included the evaluation of other immune markers (PD-1, PD-L2, and LAG-3) and their association with PD-L1. We also assessed angiogenic markers and their association with PD-L1., Results: Overall, 27.9 % of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.6 %), PD-1 and LAG-3 were positive in 17.6 % and 19.1 % respectively. None of these markers was correlated with PD-L1 expression. 66 % (45/68) expressed at least one immune marker, and 43 % (29/68) were "double-positive", as they expressed both immune and angiogenic markers. OS was significantly shorter for patients with PD-L1 positive pRCC. A multivariate analysis confirmed a significant association between PD-L1 expression and shorter overall survival (HR = 4.0, p = 0.01)., Conclusion: These results reinforce clinical data on the expected benefit of ICI in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in this multicenter cohort., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value., Methods: This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2)., Results: Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%)., Conclusions: The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Context: Computational pathology is a new interdisciplinary field that combines traditional pathology with modern technologies such as digital imaging and machine learning to better understand the diagnosis, prognosis, and natural history of many diseases., Objective: To provide an overview of digital and computational pathology and its current and potential applications in renal cell carcinoma (RCC)., Evidence Acquisition: A systematic review of the English-language literature was conducted using the PubMed, Web of Science, and Scopus databases in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42023389282). Risk of bias was assessed according to the Prediction Model Study Risk of Bias Assessment Tool., Evidence Synthesis: In total, 20 articles were included in the review. All the studies used a retrospective design, and all digital pathology techniques were implemented retrospectively. The studies were classified according to their primary objective: detection, tumor characterization, and patient outcome. Regarding the transition to clinical practice, several studies showed promising potential. However, none presented a comprehensive assessment of clinical utility and implementation. Notably, there was substantial heterogeneity for both the strategies used for model building and the performance metrics reported., Conclusions: This review highlights the vast potential of digital and computational pathology for the detection, classification, and assessment of oncological outcomes in RCC. Preliminary work in this field has yielded promising results. However, these models have not yet reached a stage where they can be integrated into routine clinical practice., Patient Summary: Computational pathology combines traditional pathology and technologies such as digital imaging and artificial intelligence to improve diagnosis of disease and identify prognostic factors and new biomarkers. The number of studies exploring its potential in kidney cancer is rapidly increasing. However, despite the surge in research activity, computational pathology is not yet ready for widespread routine use., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification and clinical management. This review discusses the histopathological disparities between intraductal and cribriform PCa from a diagnostic perspective, aiming to aid pathologists in achieving accurate diagnoses. Furthermore, it discusses the ongoing debate surrounding the different recommendations between ISUP and GUPS, which pose challenges for practicing pathologists and complicates consensus among them. Recent studies have shown promising results in integrating these pathological features into clinical decision-making tools, improving predictions of PCa recurrence, cancer spread, and mortality. Future research efforts should focus on further unraveling the biological backgrounds of these entities and their implications for clinical management to ultimately improve PCa patient outcomes.

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20-30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28-8 assay. A 2-h training module on the 28-8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR) KMT2C  = 2.54, 95%CI = [1.25,5.17], P value = .010; HR PIK3CA  = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials., (© 2023 UICC.)

Mismatch repair deficiency (d-MMR)/microsatellite instability (MSI), KRAS , and BRAF mutational status are crucial for treating advanced colorectal cancer patients. Traditional methods like immunohistochemistry or polymerase chain reaction (PCR) can be challenged by artificial intelligence (AI) based on whole slide images (WSI) to predict tumor status. In this systematic review, we evaluated the role of AI in predicting MSI status, KRAS , and BRAF mutations in colorectal cancer. Studies published in PubMed up to June 2023 were included ( n = 17), and we reported the risk of bias and the performance for each study. Some studies were impacted by the reduced number of slides included in the data set and the lack of external validation cohorts. Deep learning models for the d-MMR/MSI status showed a good performance in training cohorts (mean AUC = 0.89, [0.74-0.97]) but slightly less than expected in the validation cohort when available (mean AUC = 0.82, [0.63-0.98]). Contrary to the MSI status, the prediction of KRAS and BRAF mutations was less explored with a less robust methodology. The performance was lower, with a maximum of 0.77 in the training cohort, 0.58 in the validation cohort for KRAS , and 0.82 AUC in the training cohort for BRAF .

Objective: To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context., Design: This video article shows all the technical details of using the HMP for uterine transplantation., Setting: University., Animals: Porcine model., Intervention: Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient., Main Outcome Measures: The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus., Results: This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients., Conclusion: Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context., Competing Interests: Declaration of interests L.D. has received nonfinancial support (loan of infusion machine) from VitaSmart for the submitted work and funding from Biomedicine Agency call for tenders Graft. C.S. has nothing to disclose. K.B. reports nonfinancial support (loan of infusion machine) from VitaSmart for the submitted work. D.V.L. has nothing to disclose. S.J. has nothing to disclose. N.R.L. has nothing to disclose. E.F. has nothing to disclose. V.L. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets., Methods: We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort., Results: Unsupervised clustering identified two "TME subtypes", in each of the cohorts: the "immune-enriched" and the "immune-low". Within AXIPAP trial cohort, the "immune-enriched" cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the "immune-enriched" group (adjusted p<0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations., Conclusion: For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This "immune-enriched" group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies., Trial Registration Number: NCT02489695., Competing Interests: Competing interests: MdV-B: Research Grant: Ipsen. Board: AstraZeneca, AAA, BMS, Astellas. Travel expense: Pfizer. NR-L: Board: Ipsen, BMS, AstraZeneca. RF: Honoraria: Merck, Pfizer, Ipsen, MSD, Bayer. Board: Janssen, Merck, Pfizer. Expert: Ipsen, Janssen, Astellas. GG: Speaker bureau: Janssen, Amgen, BMS, Ipsen, AAA, AstraZeneca, Bayer, Pfizer, Merck, Astellas. Recipient my institution. Board: Janssen, Amgen, BMS, Curium, Bayer, Pfizer, Merck. Recipient my institution. Expert: BMS, Bayer, Pfizer, Merck. Recipient my institution. Travel expense: Janssen, BMS, AstraZeneca, Bayer, Pfizer Merck. Recipient: me. LG: Consulting or advisory role: BMS, MSD, Novartis, Ipsen, Janssen. CC: Consulting or advisory role: Pfizer, Novartis, BMS. FR: Consulting: Pfizer, Ipsen, BMS, MSD. AR: Consulting or advisory role: Pfizer, BMS, AstraZeneca, Roche, MSD, Ipsen. Travel expenses: Pfizer, BMS, AstraZeneca, Roche, MSD, Ipsen ; Institutional Grant: Pfizer. MG-G: Honoraria and travel expenses: Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Roche and Sanofi. BE: Advisory role: BMS, Pfizer, Novartis, Oncorena, Immunicum. Research grants: BMS, Novartis, Aveo. SN: Honoraria: Pfizer, Ipsen, MSD, BMS, Eisaï. Travel expenses: Pfizer, Ipsen, MSD. Research grant (institution): Pfizer, Ipsen. LA: Advisory role (Institution): BMS, MSD, Pfizer, Novartis, Amgen, Astellas, Ipsen, Roche, Merck, AstraZeneca, Exelixis, Peloton therapeutics, Corvus pharmaceuticals, Janssen, Eisai, 4D Pharma. Travel expenses: Merck/Pfizer. MM, JD, CP, ES-M, GF, EB, FL: no conflict., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)