BACKGROUND & AIMS:Advanced primary liver cancers remain difficult to treat after failure of first-line therapy. The 2025 French Genomic Medicine Initiative aimed to identify actionable targets for personalized treatment. METHODS:Patients with PLC progressing on systemic therapy were enrolled across eight centers. Tumor and blood samples were analyzed using whole-genome, whole-exome, and RNA sequencing to identify targetable alterations classified according to the ESCAT scale. Genomic results and potential therapies were reviewed by a molecular tumor board. RESULTS:A total of 120 patients were enrolled: 80 with hepatocellular carcinoma (HCC), 25 with cholangiocarcinoma (CCA), 9 with combined hepatocellular-cholagiocarcinoma (cHCC-CCA), 4 with fibrolamellar carcinoma, 1 with hepatic sarcoma, and 1 with hepatic epithelioid hemangioendothelioma (HEHE). Recurrent genomic alterations included TP53 (46%), TERT (44%), and CTNNB1 (20%) in HCC; TP53 (55%), ARID1A (20%), and BAP1 in CCA; and TP53 (67%), PIK3CA (22%), and ARID2 (11%) in cHCC-CCA. Among 103 interpretable genomes, 67 patients harbored at least one actionable alteration (HCC: 59%, CCA: 80%, cHCC-CCA: 78%). Thirty-one patients (22 HCC, 5 CCA, 3 cHCC-CCA, 1 HEHE, 1 hepatic sarcoma) received matched therapies: 1 ESCAT I, 2 ESCAT II, 21 ESCAT III, and 7 ESCAT IV. These patients had received prior systemic therapy, including ≥2 lines in 69% of cases. Disease control (DC; radiological response/stable disease) was achieved in 10 of 31 patients (32.3%), including 23% of HCC, 75% of CCA, and 67% of cHCC-CCA cases. DC was observed exclusively in patients treated for ESCAT I-III alterations (41.7%), with no clinical benefit in those treated for ESCAT IV alterations. Median progression-free survival was significantly longer in patients achieving DC compared with those with progressive disease (11.8 vs. 2.4 months; p = 0.009). CONCLUSIONS:Comprehensive genomic profiling in advanced PLC refractory to systemic treatment is feasible and associated with DC in a subset of pretreated patients with ESCAT I/II/III alterations. IMPACT AND IMPLICATIONS:Our research demonstrates that comprehensive genomic profiling through the French Genomic Medicine 2025 (FGM2025) initiative is feasible and clinically impactful in advanced primary liver cancers, including rare subtypes. By integrating whole-genome, whole-exome, and RNA sequencing, actionable genomic alterations were identified in nearly two-thirds of patients - well beyond the reach of standard next-generation sequencing panels. These findings provide a strong rationale for implementing early, broad molecular profiling to optimize therapeutic matching, preserve liver function, and expand access to precision medicine. Ultimately, our work highlights the transformative potential of genomics-guided strategies in improving clinical outcomes and advancing personalized care for patients with hepatobiliary malignancies.

ABSTRACT Metastatic Ewing sarcoma (MES) has a poor prognosis. This multicenter observational study provides real‐world data on treatment patterns of patients with MES in France. Treatment characteristics, outcomes such as time to next treatment (TTNT) and overall survival (OS), and prognostic factors of patients aged ≥ 12 years treated for a MES in 11 French reference network centers were retrieved from our national database. From 2008 to 2018, 156 patients with MES were included: 82 were metastatic at diagnosis (upfront metastatic cohort), 74 had developed secondary metastases after treatment of a localized disease (metastatic relapse cohort). 94% of patients received systemic treatment, with a median of three lines (1–11), 61% had at least one loco‐regional procedure and 42% of patients participated in a clinical trial in the metastatic setting. Median OS from metastatic diagnosis was 20.3 months [95% CI 14.0; 27.7] in the metastatic relapse cohort and 31.4 months [95% CI 26.5; 42.5] in the upfront metastatic cohort (p = 0.02). Median TTNT in first metastatic line was 16.8 months [95% CI 12.9; 21.3] in the upfront metastatic cohort and 7.4 months [95% CI 5.0; 11.1] in the metastatic relapse cohort, 5.8 months [95% CI 3.6; 7.3] in 2nd line and 3.8 months [95% CI 2.8; 5.7] in 3rd line, without significant difference between cohorts and treatment regimens. Patients with upfront MES have a longer OS than patients with relapsing disease, mainly due to first metastatic line dose‐dense polychemotherapy and loco‐regional procedures in selected patients. Main regimens used at relapse are associated with the same range of benefit and survival, while TKIs such as regorafenib or cabozantinib have modest activity. Inclusion in clinical trials should be prioritized.

[This corrects the article DOI: 10.1016/j.lanepe.2025.101524.].

Genetic predisposition is identified in 5–10

CellMiner Cross-Database (CellMinerCDB) is an interactive web application for integrating and analyzing molecular and pharmacological data across human cancer cell lines. Here, we detail the setup process, including installing necessary software, preparing compatible datasets, and customizing configuration files; we use sarcoma data as an example. The protocol involves data loading, software configuration, and deployment to enable univariate and multivariate analyses. For complete details on the use and execution of this protocol, please refer to Luna et al.1 and Tlemsani et al.2.

Targeting tumor suppressor genes, such as NF1, is a major challenge in cancer. Somatic NF1 mutations are found in ∼15% of lung adenocarcinoma (LUAD) cases. Still, the molecular vulnerabilities and cellular adaptations associated with these mutations remain unclear. Therefore, we aimed to study the functional consequences of NF1 loss in LUAD and its impact on the RAS/MAPK pathway, as well as potential therapeutic strategies. We established isogenic NF1-mutated cellular models (mono- and bi-allelic NF1 mutations) using CRISPR-Cas9 technology on the HBE4-E6/E7-C1 human bronchial epithelial cell line. Our studies included transcriptomic, phenotypic, and pharmacological studies, utilizing RAS/MAPK and PI3K-AKT-mTOR pathways inhibitors. Differential expression analysis was performed with the “limma” R-package with a 2 × 2 factorial design. We also computed in silico data from public drug sensitivity databases of LUAD cell lines. We tested pharmacological combinations in a patient-derived xenograft mouse (PDX) obtained from a LUAD tumor with a homozygous nonsense mutation of NF1: c.943C>T, p.(Gln315*) (Variant Allele Frequency ∼94%). We confirmed that NF1 loss-of-function led to the RAS/MAPK pathway activation, while the PI3K-AKT-mTOR pathway was not activated. We observed distinct transcriptomic clusters based on NF1 mutation status (wild-type [WT], heterozygous, and homozygous). Gene Set Enrichment Analysis found significant KRAS signaling down-regulated gene enrichment in NF1-mutated clones (q-value=0.059). Moreover, homozygous NF1-mutated lung cells exhibited more aggressive characteristics in vitro than heterozygous or WT cells: higher proliferation, higher adhesion, and greater migration capacities. In our in vitro pharmacological tests, only homozygous NF1 mutated cells were sensitive to Trametinib (a MEK inhibitor). No sensitivity was observed in these models when treated with the mTOR inhibitor AZD8055 or the PI3K inhibitor Buparlisib alone. Trametinib appeared to modulate the RAS/MAPK pathway more significantly at the transcriptomic level in cells with homozygous NF1 mutations than in NF1 WT. Trametinib and Buparlisib synergistically affected the NF1-/- model. Analysis of public drug sensitivity databases indicated that inhibitors of the RAS/MAPK and PI3K-AKT-mTOR pathways are effective against NF1-mutated LUAD cell lines. We then performed in vivo pharmacological tests on the LUAD PDX: Trametinib alone and in combination with Buparlisib resulted in significant tumor volume reductions of 72% and 84%, respectively. Collectively, these findings establish a promising possible efficacy of MEK inhibitors for LUAD patients with NF1 homozygous mutation. Jean-Stephane Giraud, Doriane Gorret, Manuela Ye, Dominique Lallemand, William C. Reinhold, Didier Decaudin, Ingrid Laurendeau, Eric Pasmant, Camille Tlemsani. NF1 mutations in lung adenocarcinoma preclinical models and potential targeted therapies: The crucial role of the RAS-MAPK pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6709.

Background:Recent clinical trials have shown that molecularly-guided treatments can improve survival in patients with cancers of unknown primary (CUP). However, the feasibility and clinical benefit of these treatments for CUP in a real-life setting remain uncertain. In France, a national multidisciplinary tumour board dedicated to patients with CUP (CUP MTB) was created in 2020, with the aims of coordinating pathological and molecular diagnostic analyses and providing a centralised expertise for therapeutic orientation. This study aimed at evaluating the diagnostic and therapeutic impact of the CUP MTB on patients with CUP in a national real-life setting. Methods:Patient and tumour characteristics, treatments and outcomes are collected prospectively. This study reports the diagnostic and therapeutic impact of all patients discussed in CUP_MTB between July 2020 and December 2023. The diagnostic impact was defined as the identification of a putative tissue of origin, and the initiation of a MTB-oriented treatment. Overall survival was estimated using the Kaplan-Meier method, and hazard ratios were calculated using Cox proportional hazard models. Findings:A total of 246 CUP patients were referred to CUP_MTB (124 females and 122 men); 187 (76%) underwent pathological and molecular characterizations as recommended by the MTB. Tumour profiling enabled the identification of a putative tissue of origin (TOO) in 130/187 (70%) patients. The most frequent TOO were gastrointestinal (n = 29; 22%), lung (n = 22; 17%), breast (n = 21; 16%), and kidney (n = 19; 15%). 149 (61%) patients received a treatment based on MTB recommendation. 111/149 (74.5%) patients received MTB-oriented treatment, including systemic treatment oriented towards the putative TOO (n = 95, 63.8%), or treatment directed towards a targetable molecular alteration (n = 16, 10.7%). 38 (25.5%) patients for whom no MTB-oriented treatment could be recommended were treated with empiric treatment according to international guidelines. The median overall survival of patients treated with MTB-oriented treatment was 18.6 (IQR = 12.0) months, compared to 11.0 (IQR = 10.5) months in patients with empiric treatment (HR = 0.61, 95% CI 0.38-0.98, p = 0.04). Interpretation:Integration of clinical, pathological and molecular data within an expert MTB is feasible in a real-life setting, enables access to molecularly guided treatments and improves survival for a large proportion of CUP patients. Our findings highlight the benefits of dedicated MTB and reference centres to improve the management of CUP. Funding:Institut Curie and the 2025 French Genomic Medicine Initiative.

Background: Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown. Patients and methods: We set up the first national retrospective study, SarcLynch, describing the pathological and clinical characteristics of sarcomas developed in patients with LS. Patients were identified from two national networks and included from 23 centres in France. Results: Eighty-one patients participated in the SarcLynch study. Sixty-seven (83 %) tumours were soft-tissue sarcomas (STS) and 14 (17 %) bone sarcomas. Among STS, 59 (88 %) showed a pleomorphic component, with undifferentiated pleomorphic sarcoma (UPS) (36 %) and pleomorphic rhabdomyosarcoma (pRMS) (21 %) being the most represented subtypes. Sarcoma was the first neoplastic event in 32 patients (40 %). Thirty-two patients (40 %) were carriers of MSH2 germline pathogenic variants. Among patients who underwent an assessment of deficient mismatch repair (dMMR) by immunohistochemistry and/or molecular biology status, 75 % were dMMR by immunohistochemistry and 45 % were microsatellite instability high (MSI-H). Eight patients received immune checkpoint inhibitors and 4 (50 %) exhibited an objective response with 3 complete radiological response including 1 patient with pathological complete response. Duration of response ranged from 6 to 20 months. Conclusions: SarcLynch, the largest multicentric series describing sarcomas developed in patients with LS, revealed an enrichment in patients with pleomorphic sarcomas - especially UPS and pRMS. This finding strongly supports screening for MMR status evaluation in these rare histotypes both for oncogenetic screening and therapeutic interest. Considering an objective response rate of 50 %, access to immunotherapy should be considered in these tumours.

BACKGROUND:Clinical practice guidelines for managing superficial non-dermatofibrosarcoma soft tissue sarcomas (NDSTS) vary depending on surgical margins. This study assessed NDSTS outcomes by margin status and re-excision (RE) in the nationwide NETSARC+ database. METHODS:This retrospective study (MR004-346) of 1773 patients used clinical data from the NETSARC database between 01/01/2010 and 12/30/2017. Analyses focused on local relapse-free survival (LRFS) and overall survival (OS). RESULTS:Pre-surgery, 31 % of patients underwent local staging with imaging, 46 % biopsy, and 17.8 % a reference center multidisciplinary tumor board (MDTB). Initial margin quality was R0, R1, R2, and unknown for 37 %, 36 %, 13 %, and 12.8 % of patients respectively. Univariate analysis positively correlated R0 surgery with preoperative biopsy (p < 0.001), adequate local imaging for tumors ≥ 5 cm (p < 0.009), case discussion within a NETSARC+ MDTB (p < 0.001), and tumor size< 5 cm (p < 0.001). Reference network surgery resulted in higher proportions of R0 margins (p < 0.001). Re-excision (RE) was performed in 9.7 %, 63 %,79 %, and 34 % of patients following initial surgery with R0, R1, R2, and unknown margins, respectively. Multivariate analysis identified several poor LRFS prognostic factors: size ≥ 5 cm (HR=1.47, p = 0.002), angiosarcoma (HR=2.95, p < 0.001), surgery outside a NETSARC network (HR=1.61, p = 0.003), old age (p < 0.001), and no final R0 margin (HR=2.60, p < 0.001). Multivariate analysis identified several poor OS prognostic factors: angiosarcoma (HR=2.03, p = 0.065), trunk/head and neck site (HR=1.57, p = 0.004), grades 2 and 3 (respectively HR=2.21, p = 0.039 and HR=4.35, p < 0.001), age (p < 0.001), and no final R0 margins (HR=2.02, p < 0.001). CONCLUSION:Sarcoma clinical practice guideline compliance was associated with better surgery quality, reduced local relapse rates, and improved survival.

Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GroupOs and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists. For various bone sarcomas including osteosarcomas, chondrosarcomas and Ewing sarcomas, we delineate tumour presentation, management strategies, and follow-up within the context of cancer predisposition syndromes. The inherited predisposition syndrome, associated with germline TP53 variants, known as the Li-Fraumeni syndrome, is the most frequent implicated in osteosarcoma cases. Other cancer predisposition syndromes, such as RB1, RECQ or CDKN2A disorders in osteosarcomas and Ollier and Maffucci diseases in chondrosarcomas, are also recognized. Additionally, we discuss rarer cancer predisposition syndromes associated with bone sarcomas and suggest tailored treatment approaches in some cancer predisposition syndromes to mitigate severe toxicities or secondary oncological events. Furthermore, we emphasize the role of identification somatic molecular variations in identifying constitutional germline variants and describe national and international screening programs, reference networks and molecular tumour boards available for collegial and collaborative management discussion. This comprehensive review provides insights into the intricate interplay between genetic predisposition, tumour biology, and therapeutic interventions in bone sarcoma patients with cancer predisposition syndrome.

Osteosarcoma (OS) and Ewing Sarcoma (ES) are the two most frequent malignant bone tumors in children, adolescents and young adults. In case of disease recurrence, both are characterized by an aggressive behaviour and a relatively poor overall survival rate, with approximately a third of patients having a long-term disease-free survival. In case of recurrent or refractory (R/R) disease, the therapeutic strategy should be discussed in multidisciplinary staff meetings with expertise in bone sarcoma management. The standard management of R/R OS depends on the disease-free interval and the number and sites of metastases and is primarily surgical in patients with isolated lung metastases or local relapse. On the other hand, conventional chemotherapy remains the standard for R/R ES and include high-dose ifosfamide, cyclophosphamide with topotecan and irinotecan with temozolomide.

Les ostéosarcomes et les sarcomes d’Ewing sont les deux tumeurs osseuses malignes les plus fréquentes chez les enfants, adolescents et jeunes adultes. En cas de récidive de la maladie, le taux de survie globale est faible, avec uniquement environ un tiers des patients ayant une survie à long terme sans maladie. En cas de maladie récurrente ou réfractaire la stratégie thérapeutique doit être discutée lors de réunions multidisciplinaires avec expertise dans la prise en charge des sarcomes osseux. La prise en charge des patients avec un ostéosarcome récurrent ou réfractaire dépend de l’intervalle sans maladie ainsi que du nombre et des sites des métastases et est principalement chirurgicale chez les patients présentant des métastases pulmonaires isolées ou une rechute locale. D’autre part, la chimiothérapie conventionnelle reste la norme pour les patients avec un sarcome d’Ewing récurrent ou réfractaire et comprend l’ifosfamide à haute dose, le cyclophosphamide avec le topotécan et l’irinotécan avec le témozolomide.

PURPOSE:No universal circulating biomarker exists for soft-tissue sarcoma (STS) and bone sarcoma. We report the translational relevance of a Droplet Digital PCR (ddPCR) assay allowing universal, specific, and dynamic detection of sarcoma-related hypermethylated ctDNA. EXPERIMENTAL DESIGN:In silico analysis (The Cancer Genome Atlas/Gene Expression Omnibus datasets, n = 8,330) identified hypermethylated DNA positions in STS/bone sarcoma, unmethylated in nonsarcoma tissues or white blood cells releasing circulating plasma cell-free DNA (cfDNA). A ddPCR assay following bisulfite conversion of cfDNA was developed. The methylation signature performances were evaluated in independent in silico cohorts (The Cancer Genome Atlas/Gene Expression Omnibus, n = 1,342). The ddPCR assay was applied to cfDNA from healthy donors, patients with metastatic STS (METASARC cohort, n = 49, 13 histotypes), and patients with STS/bone sarcoma treated with neoadjuvant chemotherapy (NEOSARC cohort, n = 42, 10 histotypes). RESULTS:A ddPCR assay targeting seven methylated genomic positions distinguished sarcoma samples from nonneoplastic mesenchymal and endothelial/liver tissues (AUC = 0.95; in silico validation set). Sensitivity allowed methylated DNA detection at a 1:1,000 dilution in genomic DNA, with a methylated allele frequency of 0.06%. ctDNA was positively detected in 45% of METASARC (22/49) and 74% of NEOSARC (31/42) patients, across all histotypes. ctDNA detection correlated with poor overall survival in METASARC patients with STS (P = 0.039). Increasing ctDNA during neoadjuvant chemotherapy was associated with poor outcomes in NEOSARC (composite criteria with poor histologic response, radiological progression, or relapse within 6 months; P = 0.0095). CONCLUSIONS:This sensitive ddPCR assay for universally methylated ctDNA enables precise detection, prognostication, and real-time monitoring of tumor burden in patients with high-grade and advanced sarcoma, regardless of histotype or origin.

Introduction Les sarcomes de tissus mous (STM) sont des tumeurs malignes du tissu conjonctif, caractérisés par une grande hétérogénéité dans leurs présentations, résultant en une variabilité des stratégies thérapeutiques entre les centres de référence. Néanmoins, les résultats cliniques issus d’un service de chirurgie orthopédique et traumatologique d’un centre hospitalo-universitaire sont peu documentés. Nous avons évalué le taux de récidive locale à 5 ans de recul des patients pris en charge selon notre stratégie locale et opérés dans notre service, labellisé pour la prise en charge des STM et des sarcomes osseux, ainsi que la survie globale et les taux de métastase et de reprises chirurgicales. Nous avons également analysé les facteurs de risque de ces évènements. Hypothèse Notre hypothèse était que nos résultats étaient relativement similaires à ceux des autres centres de référence. Matériels et méthodes Nous avons étudié 466 STM des membres et du tronc opérés de 2012 à 2019. L’âge médian des patients était de 57 ans, dont 259 hommes (56 %). Parmi eux, nous comptions 351 tumeurs naïves (75 %) ; 18 patients (4 %) avaient une atteinte ganglionnaire et 33 patients (7 %) avaient une métastase à la prise en charge initiale. Il y avait 315 sarcomes de taille supérieure à 5cm (72 %). Les sarcomes étaient localisés en profondeur pour 385 cas (83 %) et au membre inférieur proximal dans 352 cas (76 %). Nous avions 216 sarcomes (52 %) de grade 3. Les sous-types histologiques les plus fréquents étaient : le sarcome indifférencié à cellules pléiomorphes (n=104, 22 %), myxofibrosarcome (n=82, 18 %), synovialosarcome (n=45, 10 %) et liposarcome myxoïde et/ou à cellules rondes (n=42, 9 %). Concernant les traitements, 414 patients (89 %) ont eu une chirurgie conservatrice, 261 patients (56 %) ont eu une radiothérapie, et 138 patients (30 %) ont eu une chimiothérapie. Résultats À 5 ans de recul, le taux de récidive locale était de 14 % (intervalle de confiance à 95 % [IC 95 %]=10–18 %). Les facteurs de risque étaient le mode de présentation non naïf (hazard ratio [HR]=1,80, IC 95 %=1,04–3,11, p=0,037), le caractère superficiel de la tumeur (HR=2,14, IC 95 %=1,20–3,83, p=0,01), le grade 3 (HR=1,86, IC 95 %=1,22–2,83, p=0,004), les limites de résection chirurgicale positives (HR=2,47, IC 95 %=1,44–4,24, p=0,001) et la réalisation d’une chimiothérapie (HR=0,51, IC 95 %=0,30–0,87, p=0,014). La survie globale était de 60 % (IC 95 % 55–66 %). L’incidence des métastases était de 28 % (IC 95 % 23–33 %). Enfin, le taux de reprises chirurgicales était de 40 % (IC 95 % 36–45 %). Conclusion Dans notre service universitaire de chirurgie orthopédique et traumatologique, les résultats étaient relativement comparables à ceux de la littérature issus des autres centres spécialisés, à orientation oncologique exclusive ou non. Niveau de preuve IV ; étude rétrospective.

Sarcomas frequently affect adolescent girls and young women, for whom future fertility is a critical concern. The urgency of initiating treatment-due to rapid tumor progression and the need for extensive diagnostic evaluation-often limits the window for fertility preservation prior to chemotherapy. However, emerging evidence indicates that gonadotoxicity is variable, and ovarian function may be preserved in a substantial number of cases. This observational cohort study evaluates the feasibility, timing, and clinical relevance of fertility preservation in young women treated for high-grade sarcomas or desmoid tumors at Cochin Hospital, AP-HP (Paris, France), with a focus on long-term ovarian function and reproductive outcomes. Among 59 patients (median age at first oncology consultation, 24.3 years), 13 underwent oocyte or ovarian tissue cryopreservation before or early during treatment. Therapy regimens included alkylating and non-alkylating chemotherapies, radiotherapy, or combinations thereof. At last follow-up, 49 women were alive, and 27 had experienced relapse or progression. Among 26 patients assessed for post-treatment ovarian function (median follow-up 62 months), 77% resumed menstruation, 27% conceived naturally, 78% of those actively attempting pregnancy were naturally successful, and 19% gave birth. No patient used cryopreserved oocytes or ovarian tissue. One patient underwent fertility preservation after therapy. These results suggest that systematic fertility preservation may not be mandatory for all patients and that spontaneous ovarian function recovery is common. The observed pregnancy outcomes underscore the importance of personalized, patient-centered fertility counseling based on tumor characteristics and treatment modalities.

La recherche translationnelle, pont entre recherche fondamentale et clinique, constitue un élément crucial de l’innovation en oncologie. Cependant, son intégration dans la formation des internes reste peu structurée. Le programme TRANSFORM-O a ainsi été développé par la Société française du cancer en association avec le Collège national des enseignants en cancérologie afin d’initier des internes en oncologie à la conception d’essais cliniques intégrant une dimension translationnelle. Seize internes en oncologie ont participé à ce séminaire via un compagnonnage par quinze experts spécialistes de domaines distincts. Les internes ont été répartis en groupes de quatre selon quatre thématiques : biomarqueurs innovants, phases précoces, radiomique et immunothérapie. Le programme s’est déroulé sur un week-end, avec des temps dédiés à la formation, à l’élaboration du projet de recherche et à une restitution orale. Chaque groupe a conçu un projet collaboratif de recherche clinique fictif associé à un projet de recherche translationnelle ancillaire. Une évaluation par questionnaire (échelle de Likert) a été réalisée à l’issue du programme. Le taux de satisfaction global de ce projet était élevé (4,80 et 4,72 sur cinq, internes et seniors, respectivement). Cette initiative a donc montré la faisabilité et la pertinence d’une initiation précoce à la recherche translationnelle en Cancérologie. Elle pourrait être adaptée à d’autres spécialités médicales. L’impact de cette formation ponctuelle sur le parcours professionnel des internes nécessitera d’être évalué, notamment son applicabilité à un public plus large.

Translational research, a bridge between basic and clinical research, is a key component of innovation in oncology. However, its integration into medical residency training remains poorly structured. The TRANSFORM-O program was therefore developed by the Société Française du Cancer in association with the Collège National des Enseignants en Cancérologie to introduce oncology residents to the design of clinical trials incorporating a translational research component. Sixteen oncology residents have attended this seminar through mentorship by fifteen experts from various specialties. The residents were divided into four groups according to four predefined topics: innovative biomarkers, early-phase trials, radiomics, and immunotherapy. The program took place over a weekend and included dedicated sessions for training, project development, and oral presentations. Each group designed a collaborative, fictitious clinical research project combined with an ancillary translational research component. A post-program evaluation was conducted using a Likert scale questionnaire. The overall satisfaction level with the program was high (4.80 and 4.72 out of five; residents and mentors, respectively). This initiative demonstrated both the feasibility and relevance of early exposure to translational research in oncology. It could be adapted to other medical specialties. The long-term impact of such training on residents' career paths remains to be assessed, including its broader applicability.

INTRODUCTION:Soft tissue sarcomas (STS) are malignant tumors of connective tissue, characterized by a wide heterogeneity in their presentations, resulting in variable therapeutic strategies between reference centers. However, clinical outcomes from an orthopedic and trauma surgery department of university hospitals are poorly documented. We evaluated the 5-year local recurrence rate of patients managed according to our local strategy and operated in our department, which is certified for the management of both soft tissues and bone sarcomas. We also assessed overall survival, metastasis and reoperation rates, as well as risk factors associated with these events. HYPOTHESIS:Our hypothesis was that our results were relatively similar to those from other reference centers. MATERIALS AND METHODS:We analyzed 466 cases of STS of the limbs and trunk operated on between 2012 and 2019. The median patient age was 57 years, including 259 men (56%). Among them, 351 tumors (75%) were treatment-naïve; 18 patients (4%) had lymph node involvement, and 33 patients (7%) presented with metastases at initial management. There were 315 sarcomas larger than 5 cm (72%). Sarcomas were located deep in 385 cases (83%) and in the proximal lower limb in 352 cases (76%). A total of 216 sarcomas (52%) were grade 3. The most frequent histologic subtypes were undifferentiated pleomorphic sarcoma (n = 104, 22%), myxofibrosarcoma (n = 82, 18%), synovial sarcoma (n = 45, 10%), and myxoid and/or round cell liposarcoma (n = 42, 9%). Regarding treatments, 414 patients (89%) underwent limb-sparing surgery, 261 (56%) received radiotherapy, and 138 (30%) received chemotherapy. RESULTS:At 5 years of follow-up, the local recurrence rate was 14% (95% confidence interval [CI] = 10-18%). Independent risk factors were non-naïve presentation (hazard ratio [HR] = 1.80, 95% CI = 1.04-3.11, p = 0.037), superficial tumor location (HR = 2.14, 95% CI = 1.20-3.83, p = 0.01), grade 3 histology (HR = 1.86, 95% CI = 1.22-2.83, p = 0.004), positive surgical margins (HR = 2.47, 95% CI = 1.44-4.24, p = 0.001), and administration of chemotherapy (HR = 0.51, 95% CI = 0.30-0.87, p = 0.014). Overall survival was 60% (95% CI = 55-66%). The incidence of metastases was 28% (95% CI = 23-33%), and the rate of reoperations was 40% (95% CI = 36-45%). CONCLUSION:In our university orthopedic and trauma surgery department, the oncological outcomes were comparable to those reported in the literature from other specialized centers, whether with exclusively oncologic activity or not. LEVEL OF EVIDENCE:IV; retrospective study.