Search

Background: The modified docetaxel, cisplatin, and fluorouracil (mDCF) regimen has shown efficacy and safety as first-line treatment for advanced squamous cell carcinoma of the anus, making it a standard regimen. Inhibitors of programmed cell death protein 1 and its ligand, such as pembrolizumab, nivolumab, retifanlimab, avelumab, and atezolizumab, have shown some antitumour activity as monotherapy in advanced squamous cell carcinoma of the anus that is refractory to chemotherapy. This phase 2 study evaluated the combination of mDCF and atezolizumab as first-line treatment in advanced squamous cell carcinoma of the anus., Methods: In this randomised, open-label, non-comparative, phase 2 study, participants from 21 centres (academic, private, and community hospitals and cancer research centres) across France with chemo-naive, metastatic, or unresectable locally advanced recurrent squamous cell carcinoma of the anus, aged 18 years or older, and with an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly allocated (2:1) to receive either atezolizumab (800 mg intravenously every 2 weeks up to 1 year) plus mDCF (eight cycles of 40 mg per m 2 docetaxel and 40 mg per m 2 cisplatin on day 1 and 1200 mg per m 2 per day of fluorouracil for 2 days, every 2 weeks intravenously; group A) or mDCF alone (group B). Randomisation was done centrally using a minimisation technique and was stratified by age (<65 years vs ≥65 years) and disease status. The primary endpoint was investigator-assessed 12-month progression-free survival in the modified intention-to-treat population in group A (35% for the null hypothesis and 50% for the alternative hypothesis). This trial is registered with ClinicalTrials.gov, NCT03519295, and is closed to new participants., Findings: 97 evaluable participants (64 in group A and 33 in group B) were enrolled between July 3, 2018, and Aug 19, 2020. The median follow-up was 26·5 months (95% CI 24·8-28·4). The median age of participants was 64·1 years (IQR 56·2-71·6), and 71 (73%) were female. 12-month progression-free survival was 45% (90% CI 35-55) in group A and 43% (29-58) in group B. In participants with a PD-L1 combined positive score of 5 or greater, 12-month progression-free survival was 70% (95% CI 47-100) in group A and 40% (19-85) in group B (interaction p=0·051) Both groups showed high compliance. Adverse events of grade 3 or higher were observed in 39 (61%) participants in group A and 14 (42%) in group B. The most common grade 3-4 adverse events were neutropenia (nine [14%] participants in group A vs five [15%] in group B), anaemia (nine [14%] vs one [3%]), fatigue (three [5%] vs four [12%]), and diarrhoea (seven [11%] vs one [3%]). Serious adverse events occurred in 16 (25%) participants in group A and four (12%) in group B, and these were mDCF-related in seven (11%) participants in group A and four (12%) in group B. Atezolizumab-related serious adverse events occurred in nine (14%) participants in group A, including grade 2 infusion-related reaction in three (5%), grade 3 infection in two (3%), and grade 2 colitis, grade 3 acute kidney injury, grade 3 sarcoidosis, and a grade 4 platelet count decrease each in one participant (2%). There were no treatment-related deaths., Interpretation: Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies., Funding: GERCOR, Roche., Competing Interests: Declaration of interests Genentech provided atezolizumab for the study. SK reports consultancy, advisory roles, and honoraria from Amgen, BeiGene, Boehringer Ingelheim, Merck, MSD, Pfizer, and Servier; and research funding from Boehringer Ingelheim, Bristol Myers Squibb, Novartis, and Roche. FG reports consultancy for Roche, MSD, Merck Serono, Brenus, Engetix, and Odimma; research grants from AstraZeneca, Roche Genentech, Amgen, XBiotech, and Springworks; and travel or accommodation from Amgen, MSD, Roche, and Servier. CdlF reports honoraria from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Incyte Biosciences, Ipsen, Lilly, Merck Serono, MSD, Pierre Fabre Oncologie, Pfizer, Roche, Sanofi-Aventis, and Servier. ES reports consultancy, advisory roles, and honoraria from Amgen, Astellas, BeiGene, Bristol Myers Squibb, Daichi, Merck, MSD, Pierre Fabre, and Servier; and travel or accommodation from Bristol Myers Squibb, MSD, Pierre Fabre, and Servier. DT reports consulting or advisory board fees from AstraZeneca, Sanofi, Amgen, MSD, BMS, Roche, Servier, and Pierre Fabre; and research funding from Pierre Fabre and Sandoz. OB reports honoraria for speaker or advisory roles from Astellas, Merck Serono, Amgen, Servier, Pierre Fabre, Apmonia Therapeutics, Deciphera, and MSD. DV reports consulting fees from Apmonia Therapeutics, Cellprothera, Novartis, Incyte, Veracyte, and Lysarc. FB reports honoraria for speaker or advisory roles from Astellas, Servier, Incyte, Pierre Fabre, BMS, AstraZeneca, Owkin, and MSD. JT reports honoraria for speaker or advisory roles from Astellas, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, BMS, AstraZeneca, Novartis, Takeda, and MSD. MBA reports honoraria for speaker or advisory roles from Bayer, Incyte, Deciphera, Merck, Servier, BMS, Pierre Fabre, and Amgen. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Variant histology or divergent differentiation (VH/DD) of urothelial carcinoma (UC) may impact outcomes after neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer. Our aim was to assess the pathological response and progression-free survival (PFS) of patients with VH/DD in the prospective VESPER clinical trial., Materials and Methods: This post hoc study included 300 NAC-treated patients with available transurethral diagnostic slides. Presence and percentage of VH/DDs were reviewed. For pathological response, logistic regression models were computed to measure association with VH/DD. For PFS, the associations were estimated in Cox proportional hazard regression model. All models were adjusted for randomization arm., Results: VH/DD was identified in 177/300 patients (59%) and was predominant (≥50%) in 85/177. Compared to pure UC, VH/DD (≥10% or ≥50%) was not associated with a difference in proportion of complete pathological response (ypT0N0; OR adjusted: 0.79, 95% CI 0.49-1.29), downstaging (≤ypT1N0; OR adjusted: 0.62, 95% CI 0.37-1.02), or with an increased hazard of PFS (HR adjusted: 1.24, 95% CI 0.83-1.85). However, comparing specific VH/DD to pure UC, nested subtype was associated with decreased odds of complete pathological response (OR adjusted: 0.33, 95% CI 0.12-0.88) and downstaging (OR adjusted: 0.30, 95% CI 0.13-0.74), and an increased hazard of PFS was observed for UC with ≥ 50% squamous differentiation (HR adjusted: 2.11, 95% CI 1.01-4.38) or micropapillary subtype (HR adjusted: 2.03, 95% CI 0.98-4.22)., Conclusions: In the VESPER trial, we did not observe evidence for association of VH/DD with outcomes after NAC, but the specific presence of a predominant squamous differentiation or micropapillary subtype may be associated with shorter PFS.

Background: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database., Methods: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions., Results: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis., Conclusion: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations., Methodology: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS)., Results: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey., Conclusion: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: COVID-19 may have negatively impacted the mental health of front-line healthcare workers, including general practitioners (GPs). This study sought to assess the psychological impact (stress, burnout and self-efficacy) of the COVID-19 outbreak in French GPs., Methods: We carried out a postal-based survey of all GPs who worked in the French region of Normandy (departments of Calvados, Manche and Orne) from the exhaustive database of the Union Régionale des Médecins libéraux (URML Normandie) as of 15th April 2020 (one month after the first French COVID-19 sanitary lockdown). The second survey was conducted four months later. Four validated self-report questionnaires were used at both inclusion and follow-up: Perceived Stress scale (PSS), Impact of Event Scale-revised (IES-R), Maslach Burnout Inventory (MBI) and General Self-Efficacy scale (GSE). Demographic data were also collected., Results: The sample consists of 351 GPs. At the follow-up, 182 answered the questionnaires (response rate: 51.8%). The mean scores of MBI significantly increased during follow-up [Emotional exhaustion (EE) and Personal accomplishment, P<0.01]. Higher burnout symptoms were found at the 4-month follow-up in 64 (35.7%) and 86 (48.0%) participants (43 and 70 participant at baseline), according respectively to EE and depersonalisation scores (P=0.01 and 0.09, respectively)., Conclusion: This is the first longitudinal study that has shown the psychological impact of COVID-19 in French GPs. Based on validated a self-report questionnaire, burnout symptoms increased during follow-up. It is necessary to continue monitoring psychological difficulties of healthcare workers especially during consecutive waves of COVID-19 outbreak., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated., Methods: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE., Results: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53-0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE., Conclusions: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm.

Peptidoglycan is a carbohydrate with a cross-linked structure that protects the cytoplasmic membrane of bacterial cells from damage. The mechanism of peptidoglycan biosynthesis involves the main synthesizing enzyme glycosyltransferase MurG, which is known as a potential target for antibiotic therapy. Many MurG inhibitors have been recognized as MurG targets, but high toxicity and drug-resistant Escherichia coli strains remain the most important problems for further development. In addition, the discovery of selective MurG inhibitors has been limited to the synthesis of peptidoglycan-mimicking compounds. The present study employed drug discovery, such as virtual screening using molecular docking, drug likeness ADMET proprieties predictions, and molecular dynamics (MD) simulation, to identify potential natural products (NPs) for Escherichia coli. We conducted a screening of 30,926 NPs from the NPASS database. Subsequently, 20 of these compounds successfully passed the potency, pharmacokinetic, ADMET screening assays, and their validation was further confirmed through molecular docking. The best three hits and the standard were chosen for further MD simulations up to 400 ns and energy calculations to investigate the stability of the NPs-MurG complexes. The analyses of MD simulations and total binding energies suggested the higher stability of NPC272174. The potential compounds can be further explored in vivo and in vitro for promising novel antibacterial drug discovery., (© 2024. The Author(s).)

Background: Surgical site infection (SSI) is the most frequent and severe adverse event after surgery. Among preventive measures, the preoperative skin preparation (PSP) is known to be heterogeneously implemented in routine practice. A prerequisite would be the actual incorporation of guidelines in French surgical local protocols., Aim: To assess whether PSP recommendations have been incorporated in local protocols and to identify the reasons for the non-incorporation., Methods: An online survey was proposed to all infection control teams (ICTs) in facilities participating in the French national surveillance and prevention of SSI network Spicmi. The reference recommendations were based on the French Society for Hospital Hygiene guidelines., Findings: In all, 485 healthcare facilities completed the questionnaire. The incorporation of recommendations in the facility protocol varied between 30% and 98% according to the recommendation. The measures most frequently incorporated were antisepsis with an alcoholic product and cessation of systematic hair removal. The least frequently incorporated were the use of plain soap for preoperative shower and the non-compulsory skin cleaning in the operating room. Barriers reported were either specific to PSP (e.g. 'Concern about an increase of SSI', 'Scepticism about recommendations', 'Force of habit') or non-specific (e.g. 'The protocol not yet due to be updated')., Conclusion: We suggest that although some major prevention measures have been incorporated in the local protocol of most facilities, local protocols still frequently include some non-evidence based former recommendations. Communication about evolution of SSI rates, diffusion of guidelines by learned societies, and exchange with judiciary experts could make clear the conditions for applying recommendations., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Extreme prematurity (birth before 26 weeks of gestation), presents complex challenges and can lead to various complications. Survival rates of extremely preterm infants are lower in France than in other countries. The choice between active and palliative care is decisive in managing these births., Objective: To conduct an observational study focused on factors associated with perinatal management, mortality, and morbidity outcomes among extremely preterm births in a regional perinatal network., Methods: We undertook a retrospective, multicenter study within the western Normandy perinatal network, encompassing live births between 23 0 /6 and 25 6/6 weeks from 2015 to 2019. Data were extracted from the perinatal network database and medical records., Results: One hundred and seven infants born from 94 women were included. In the antenatal period, 79 were exposed to corticosteroids, 66 to magnesium sulfate, and 67 to antibiotics. Active care at birth was provided to 84 neonates of whom 42 survived. In total, 65 infants died. Among the 42 surviving neonates, 9 experienced no severe morbidity, 29 displayed one and 4 exhibited two criteria of severe morbidity. Active care was associated with gestational age. Neonatal survival was correlated with antenatal exposure to antibiotics and magnesium sulfate as well as with postnatal corticosteroids. We found no significant association between mortality and gestational age at birth., Conclusion: Prognostic factors must be weighed to discuss active antenatal care which is crucial for survival of extremely preterm neonates. Cooperation between obstetricians and neonatal caregivers is a cornerstone on a regional perinatal network scale., Competing Interests: Declarations of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This pilot study reveals a higher prevalence of obstructive sleep apnea syndrome (OSAS) in patients treated for oropharyngeal squamous cell carcinoma with radiotherapy compared to the general population. OSAS indicators such as the Epworth Sleepiness Scale seem insufficient in the diagnostic approach to OSAS in this population and systematic screenings should be considered., 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 Elsevier B.V. All rights reserved.)

Accessibility to care is a major public health issue. Various tools to assess it are available, but they do not solve the problem of scale. Moreover, accessibility is a multidimensional concept that is not taken into account with current tools. The SCALE index aims to overcome these two limitations by proposing a synthetic measure on a more precise scale than the administrative unit or the sub-municipal scale. Under the assumption of access to care facilities for all and access to the nearest facilities, the potential accessibility distance was calculated for each couple (residential area, accessible facilities). This was defined as the average distance by road that the population has to travel to access care. To take the availability of resources into account, these distances were weighted by the theoretical pressure on the facilities. The SCALE index was then calculated using a linear combination of the distances of potential accessibility to care facilities It highlights differences in accessibility at the national and regional scale. Using this index, it was possible to provide maps for all French regions and the major cities in a story-map. The major conurbation around Paris and the main urban centers has high accessibility. Low accessibility forms a "Y" shape. In conclusion, the SCALE index measures accessibility at the scale of a small geographic unit taking the proximity and the availability of health professionals into account. It is also possible to take into account the diversity of accessibility in a given territory.

Introduction: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive in unselected mCRPC, the literature suggests an anti-tumoral activity in mCRPC with HHR gene alterations. We aimed to assess the efficacy of carboplatin monotherapy in mCRPC patients with HRR deficiency., Methods: This prospective multicenter single-arm two-stage phase II addressed mCRPC men with HRR somatic and/or germline alterations, pretreated with ⩾2 taxane chemotherapy regimens and one androgen receptor pathway inhibitor. Prior PARPi treatment was allowed. Enrolled patients received intravenous carboplatin (AUC5) every 21 days for 6-9 cycles. The primary endpoint was the best response rate according to adapted PCWG3 guidelines: radiological response (RECIST 1.1 criteria) and/or biological response [⩾50% prostate-specific antigen (PSA) decline]., Results: A total of 15 out of 16 enrolled patients started carboplatin treatment. Genomic alterations were identified for BRCA2 ( n  = 5), CDK12 ( n  = 3), ATM ( n  = 3) CHEK2 ( n  = 2), CHEK1 ( n  = 1), and BRCA1 ( n  = 1) genes. Objective response (partial biological response + stable radiological response) was achieved in one patient (6.7%), carrying a BRCA2 mutation and not pre-treated with PARPi; stable disease was observed for five patients (33.5%). Among seven patients (46.7%) with previous PARPi treatment, four patients (57.1%) had a stable disease. The median progression-free and overall survivals were 1.9 [95% confidence interval (95% CI), 1.8-9.5] and 8.6 months (95% CI, 4.3-19.5), respectively. The most common severe (grade 3-4) treatment-related toxicities were thrombocytopenia (66.7%), anemia (66.7%), and nausea (60%). Overall, 8 (53.3%) patients experienced a severe hematological event., Conclusion: The study was prematurely stopped as pre-planned considering the limited activity of carboplatin monotherapy in heavily pre-treated, HHR-deficient mCRPC patients. Larger experience is needed in mCRPC with BRCA alterations., Trial Registration: NCT03652493, EudraCT ID number 2017-004764-35., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Chronic kidney disease-associated pruritus (CKD-aP) is a disabling symptom which is frequent and often underestimated. Pa-MRC has a negative impact on quality of life, and is frequently accompanied by sleep disorders and depression. The approval of difelikefalin – a kappa opioid receptor agonist – in this indication requires updated recommendations. As a first step, secondary causes of pruritus without skin lesions must be ruled out, and general measures taken (emollients, psychological support, optimization of dialysis, normalization of serum calcium, phosphate and PTH in the range proposed by the KGIDO guidelines, treatment of iron deficiency). A therapeutic test with a non-sedating oral antihistamine may be proposed. If this test is negative, Pa-MRC must be strongly suspected, and its intensity (WI-NRS scale) and impact on quality of life assessed. In the case of mild Pa-MRC (WI-NRS ≤ 3), only general measures are implemented. If Pa-MRC is moderate to severe (WI-NRS ≥ 4), specific treatment with difelikefaline can be initiated for 6 months in addition to general measures. At 3 months, if the response is complete (WI-NRS score ≤ 1) or partial (decline ≥ 3 points), treatment is continued. At 6 months, if the response is complete, treatment may be discontinued with the patient’s agreement; treatment is maintained if the response is partial. At 3 or 6 months, if response is insufficient (decline < 3 points) and/or in the event of intolerance, treatment is discontinued and an alternative treatment (e.g., gabapentinoids, UVB) may be considered after dermatological consultation.

Background: RT-induced hyalinization/fibrosis was recently evidenced as a significant independent predictor for complete response to neoadjuvant radiotherapy (RT) and survival in patients with soft tissue sarcoma (STS). Purpose: Non-invasive predictive markers of histologic response after neoadjuvant RT of STS are expected. Materials and Methods: From May 2010 to April 2017, patients with a diagnosis of STS who underwent neoadjuvant RT for limb STS were retrieved from a single center prospective clinical imaging database. Tumor Apparent Diffusion Coefficients (ADC) and areas under the time-intensity perfusion curve (AUC) were compared with the histologic necrosis ratio, fibrosis, and cellularity in post-surgical specimens. Results: We retrieved 29 patients. The median ADC value was 134.3 × 10 -3 mm 2 /s. ADC values positively correlated with the post-treatment tumor necrosis ratio ( p = 0.013). Median ADC values were lower in patients with less than 50% necrosis and higher in those with more than 50% (120.3 × 10 -3 mm 2 /s and 202.0 × 10 -3 mm 2 /s, respectively ( p = 0.020). ADC values higher than 161 × 10 -3 mm 2 /s presented a 95% sensitivity and a 55% specificity for the identification of tumors with more than 50% tumor necrosis ratio. Tumor-to-muscle AUC ratios were associated with histologic fibrosis ( p = 0.036). Conclusions: ADC and perfusion AUC correlated, respectively, with radiation-induced tumor necrosis and fibrosis.

Background: Ovarian cancer is rare with a poor prognosis and few established risk factors. Hormones and reproductive factors significantly impact its development, suggesting a potential link with endocrine disrupters., Methods: In the AGRICAN cohort, 59 391 female farmers completed data on lifelong agricultural exposures and reproductive life. Cox models with attained age as timescale (HR and 95% CI) were used. The role of hormonal factors as potential confounders was considered along with specific time windows for exposure (childhood, puberty and menopause). Female farmers were the reference group (for the principal analyses)., Results: Between enrolment (2005-2007) and the end of follow-up (31 December 2017), 262 incident ovarian cancers were identified. An increased risk was observed for females involved in pigs (HR=2.12 (95% CI 1.27 to 3.52)) including during puberty (HR=1.83 (95% CI 1.13 to 2.94)), fruit-growing (HR=2.17 (95% CI 1.09 to 4.30)) and potato seed treatment (HR=2.81 (95% CI 1.29 to 6.09)). Conversely, females born on farms growing grain cereals (HR=0.64 (95% CI 0.46 to 0.90)) or pig-breeding (HR=0.78 (95% CI 0.55 to 1.12)) presented a reduced risk of ovarian cancer. Triazine herbicide exposure was not associated with ovarian cancer. The effect of agricultural exposures remained unchanged in multivariate models considering contraception, parity, puberty age, menopause age and body mass index., Conclusion: This study is the first to assess the association between specific agricultural exposures and ovarian cancer comprehensively. Some of the positive associations observed suggest that some pesticide exposure (especially during puberty) could play a role in the development of ovarian cancer. On the other hand, agricultural exposure during early life could have a protective effect, as observed for lung cancer among farmers. Finally, we did not confirm the previous putative effect of exposure to triazine herbicides., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Research Question: What are current practices of post-treatment fertility preservation in male childhood cancer survivors (CCS) who have not benefitted from pre-therapeutic fertility preservation in France and other European countries?, Design: A survey was conducted of all fertility preservation centres in France (n = 30) and European fertility specialists (n = 9) in five European countries. Eight clinical cases and 40 questions were included to assess the effect of age at diagnosis, type of treatment (alkylating-agents, orchidectomy, testicular radiotherapy) and sperm parameters on the probability of a post-treatment fertility preservation proposal. Demographic characteristics of the responding practitioner were also collected., Results: Post-treatment sperm cryopreservation was proposed by 100% of fertility specialists in cases of severe oligoasthenoteratozoospermia, 77-88% in cases of moderate oligoasthenoteratozoospermia and in 65-77% in cases of sperm motility and vitality impairment. In cases of normal sperm parameters, 27-54% of fertility specialists would propose post-treatment sperm cryopreservation. These results did not differ significantly according to the type of treatment received or to responder-related factors. Practices of European specialists were also guided by sperm parameter results; 44-67% of specialists responding that they would propose sperm cryopreservation in cases of moderate to severe sperm parameter alterations., Conclusion: Post-treatment semen analysis could be widely proposed to CCS who have not benefitted from pre-therapeutic fertility preservation. Post-treatment fertility preservation could be proposed in cases of persistent moderate to severe sperm parameter alterations. Guidelines would be important to homogenize practices and to encourage oncologists to refer CCS for fertility assessments., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Systematic screening for pancreatic cancer in high risk individuals is justified by the poor prognosis of the majority of cases diagnosed at a symptomatic stage that are mostly advanced and unresectable Individual risk assessment is based on both genetic data and family history. The screening of a panel of susceptibiility genes should be offered to any affected individual when a genetic predisposition is suspected. An international consortium has proposed a definition of the at risk population, candidate for screening, and there is a consensus on the target lesions of this screening: early adenocarcinoma and benign lesions with a high potential for malignant transformation: Intraductal Papillary Mucinous Neopasm (IPMN) and Pancreatic Intraepithelial Neoplasia (PanIN) with high-grade dysplasia. Its modalities currently consist of an annual pancreatic MRI and/or endoscopic ultrasound (EUS), associated with screening for diabetes mellitus. The main limitation of screening, the effectiveness of which has not yet been demonstrated, is its lack of sensitivity, which results in a non-negligible rate of interval cancers and sometimes advanced diagnoses. Insufficient specificity is also imperfect, in particular with regard to benign lesions with a low potential for degeneration, and can lead to the proposal of unjustified surgeries. This situation makes the future integration of new imaging techniques and promising new biological approaches that are being explored highly desirable., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Sexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes., Methods: Patients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics., Results: Nearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years' follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR) poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; OR sexual inactivity 9.94 (95% CI 8.84-11.18), OR poor sexual function 9.75 (95% CI 8.67-10.95), OR poor sexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [OR poor body image 1.15 (95% CI 1.01-1.31); OR sexual inactivity 1.19 (95% CI 1.02-1.39), OR poor sexual function 1.17 (95% CI 1.01-1.37), OR poor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [OR poor body image 2.00 (95% CI 1.72-2.34); OR sexual inactivity 1.66 (95% CI 1.40-1.97), OR poor sexual function 1.69 (95% CI 1.43-2.00), OR poor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified., Conclusions: Sexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors., Objectives: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose., Population: Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5-19). Patients previously received a median of 3.5 (range, 1-4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy., Results: Median number of cycles was 2 (1-24), median treatment duration was 56 days (18-714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor., Conclusion: Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing., Competing Interests: Declaration of Competing Interest Nivolumab and funding has been provided by BMS. NA has had an advisory role for Bayer and Partners Therapeutics and receives grants (institution) from Bristol Myers Squibb and drugs for a trial from Bristol Myers Squibb, Pierre Fabre, Merck, Pfizer, travel support from Roche; Speaker's Honoraria for Alection, he further has IDMC roles for Accord Healthcare. IA receives speaker’s honoraria from Alection. BG has had an advisory role for AstraZeneca and IDMC roles for trials sponsored by Roche and Novartis. Speaker's Honoraria - Bayer. PC speaker’s honoraria from Alection. NEW receives drug for a trial from Novartis, speaker’s honoraria from Alection, Eusapharma & Novartis. PL receives drug from BMS for a trial and speaker’s honoraria from Alection. MCLD, CL, AP, LW, CFC, GRV, VM and AB declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: The reform of the third cycle of medical studies in France has introduced of the "Junior Doctor" status during the concluding year of residency. We wish to evaluate its implementation for the first promotion of medical oncology residents during 2021-2022 in correlation with the published guidelines., Method: AERIO conducted a cross-sectional study among French medical oncology residents. The survey was released via social networks and emails., Results: Twenty-eight of 47 residents responded. The typical week involved one to two half-days of consultation, one dedicated to clinical research, one multidisciplinary team meetings, with the rest of time being occupied by day care (mostly) and hospitalization. Teaching and quality management activities were infrequent (monthly or less). The Junior Doctors rated their overall satisfaction at 8/10. A large majority (92.5 %) felt equipped to handle most of the situations they encountered. Almost all residents (92.9 %) had negotiated with their placement supervisor prior to the selection procedure. In one third of the cases (35.7 %), the principle of mismatch between the number of residents and the number of training sites was not respected. Only 42.9 % received training in scientific writing and 82.2 % of the residents agreed on the relevance of the post-internship training modules developed in other specialties., Conclusions: Junior doctors in medical oncology express overall satisfaction with this reform, which aligns with the recommendations. Nevertheless, certain concerns, such as selection procedure and inadequacy, along with areas requiring improvement, such as post-internship training and scientific writing, are clearly established., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported .In patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, the STIC CTC trial established that, for choosing between endocrine therapy (ET) or chemotherapy, the use of circulating tumor cell (CTC) count is noninferior to the investigator's choice in terms of progression-free survival. Here, we report overall survival (OS) results, a secondary end point. Patients were randomly assigned in a 1:1 ratio to have their first-line treatment (ET or chemotherapy) determined by investigators or CTC count (chemotherapy if ≥ 5 CTCs/7.5 mL; ET if low CTC count; CellSearch). OS was assessed at the discontinuation of follow-up. After a median follow-up of 4.7 years, 382 deaths (50.6%) had occurred among 755 patients. Median OS was 51.3 months (95% CI, 46.8 to 55.1) in the CTC arm and 45.5 months (95% CI, 40.9 to 51.1) in the standard arm (hazard ratio [HR] for death, 0.85; 95% CI, 0.69 to 1.03; P = .11). Among 189 patients (25.0%) with ET recommended by clinicians and high CTC count, chemotherapy was superior to ET (HR for death, 0.53; 95% CI, 0.36 to 0.78; P = .001). In case of a discordant estimate, OS data demonstrate the clinical utility of CTC count.

Background and Aims: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)., Method: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation., Results: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9-10.66] per 100 000 person-years, Q2 11.43 [10.48-12.47] (p < .0001), Q3 11.81 [10.82-12.89] (p < .0001), Q4 12.26 [11.25-13.37] (p < .001) and Q5 11.53 [10.57-12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407)., Conclusion: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: CA-125 alone is widely used to diagnose progressive disease (PD) in platinum-sensitive recurrent ovarian cancer (PSROC) on chemotherapy. However, there are increasing concerns regarding its accuracy. We assessed concordance between progression defined by CA-125 and RECIST using data from the CALYPSO trial., Methods: We computed concordance rates for PD by CA-125 and RECIST to determine the positive (PPV) and negative predictive values (NPV)., Results: Of 769 (79%) evaluable participants, 387 had CA-125 PD, where only 276 had concordant RECIST PD (PPV 71%, 95% CI 67-76%). For 382 without CA-125 PD, 255 had RECIST PD but 127 did not (NPV 33%, 95% CI 29-38). There were significant differences in NPV according to baseline CA-125 (≤100 vs >100: 42% vs 25%, P < 0.001); non-measurable vs measurable disease (51% vs 26%, P < 0.001); and platinum-free-interval (>12 vs 6-12 months: 41% vs 14%, P < 0.001). We observed falling CA-125 levels in 78% of patients with RECIST PD and CA-125 non-PD., Conclusion: Approximately 2 in 3 women with PSROC have RECIST PD but not CA-125 PD by GCIG criteria. Monitoring CA-125 levels alone is not reliable for detecting PD. Further research is required to investigate the survival impact of local therapy in radiological detected early asymptomatic PD., (© 2023. Crown.)

Background: Cumulative environmental exposures and social deprivation increase health vulnerability and limit the capacity of populations to adapt to climate change., Objective: Our study aimed at providing a fine-scale characterization of exposure to heat, air pollution, and lack of vegetation in continental France between 2000 and 2018, describing spatiotemporal trends and environmental hotspots (i.e., areas that cumulate the highest levels of overexposure), and exploring any associations with social deprivation., Methods: The European (EDI) and French (FDep) social deprivation indices, the normalized difference vegetation index, daily ambient temperatures, particulate matter (PM 2.5 and PM 10 ), nitrogen dioxide, and ozone (O 3 ) concentrations were estimated for 48,185 French census districts. Reference values were chosen to characterize (over-)exposure. Hotspots were defined as the areas cumulating the highest overexposure to temperature, air pollution, and lack of vegetation. Associations between heat overexposure or hotspots and social deprivation were assessed using logistic regressions., Results: Overexposure to heat was higher in 2015-2018 compared with 2000-2014. Exposure to all air pollutants except for O 3 decreased during the study period. In 2018, more than 79% of the urban census districts exceeded the 2021 WHO air quality guidelines. The evolution of vegetation density between 2000 and 2018 was heterogeneous across continental France. In urban areas, the most deprived census districts were at a higher risk of being hotspots (odds ratio (OR): 10.86, 95% CI: 9.87-11.98 using EDI and OR: 1.07, 95% CI: 1.04-1.11 using FDep)., Impact Statement: We studied cumulative environmental exposures and social deprivation in French census districts. The 2015-2018 period showed the highest overexposure to heat between 2000 and 2018. In 2018, the air quality did not meet the 2021 WHO guidelines in most census districts and 8.6 million people lived in environmental hotspots. Highly socially deprived urban areas had a higher risk of being in a hotspot. This study proposes for the first time, a methodology to identify hotspots of exposure to heat, air pollution, and lack of vegetation and their associations with social deprivation at a national level., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Treatment summaries and a personalized survivorship care plans based on internationally approved, organ-specific follow-up care recommendations are essential in preserving the health and quality of life for cancer survivors. Cohorts made up of survivors of childhood cancer have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among former patients. New treatment protocols are needed to enhance survival and reduce the potential risk and severity of late effects, and working with treatment databases is crucial in doing so., Construction and Content: In the GOCE (Grand Ouest Cancer de l'Enfant [Western Region Childhood Cancer]) network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. Its name emphasizes the tool's goal, referring to 'logiciel' (the French word for software) that focuses on the period "after" the acute phase. This tool is hosted on a certified health data server. Several interfaces have been developed that can be used depending on the user's profile. Here we present this innovative co-constructed tool that takes national aspects into account, including the results of the feasibility/satisfaction study and its perspective., Utility and Discussion: The database contains data relating to 2558 patients, with samples from 1702 of these (66.54%) being held in a tumor bank. The average year in which treatment started was 2015 (ranging from December 1967 to November 2022: 118 patients were treated before 2012 and registered retrospectively when seen in long-term follow-up consultations or for another cancer since November 2021). A short questionnaire was distributed to healthcare professionals using the tool (physicians and research associates or technicians, n = 14), of whom 11 answered and were all satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients who were over 15 years old, affected by the disease within the last 5 years, and had agreed to test it. Their opinions were collected by their doctor by e-mail, telephone, or during a consultation in an open-ended question and a non-directive interview. All patients were satisfied with the tool, with interest in testing it in the long term. Some former patients found that the tool provided them with some ease of mind; one, for instance, commented: "I feel lighter. I allow myself to forget. I know I will get a notification when the time comes.", Conclusions: Freely available to all users, LOG-after: (1) provides help with determining personalized survivorship care plans for follow-up; (2) builds links with general practitioners; (3) empowers the patient; and (4) enables health data to be exported for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE., (© 2024. The Author(s).)

Background: Missing covariates are common in observational research and can lead to bias and loss of statistical power. Limited data regarding prognostic factors of survival outcomes of sarcomas in irradiated fields (SIF) are available. Because of the long lag time between irradiation of first cancer and scarcity of SIF, missing data are a critical issue when analyzing long-term outcomes. We assessed prognostic factors of overall (OS), progression-free (PFS), and metastatic-progression-free (MPFS) survivals in SIF using three methods to account for missing covariates., Methods: We relied on the NETSARC French Sarcoma Group database, Cox (OS/PFS), and competitive hazards (MPFS) survival models. Covariates investigated were age, sex, histological subtype, tumor size, depth and grade, metastasis, surgery, surgical resection, surgeon's expertise, imaging, and neo-adjuvant treatment. We first applied multiple imputation (MI): observed data were used to estimate the missing covariate. With the missing-data modality approach, a category missing was created for qualitative variables. With the complete-case (CC) approach, analysis was restricted to patients without missing covariates., Results: CC subjects ( N = 167; 33%) presented more often with soft-tissue sarcoma ( versus visceral sarcoma) and grade I-II tumors as compared to the 504 eligible cases. With MI ( N = 504), factors associated with the worst outcome included metastasis ( p = 0.04) and R1/R2 resection ( p < 0.001) for OS; higher grade/non-gradable tumors ( p = 0.002) and R1/R2 resection ( p < 0.001) for PFS; and metastasis ( p = 0.01) for M-PFS. The 'missing-data modality' approach ( N = 504) led to different associations, including significance reached due to variables with the modality 'missing'. The CC analysis led to different results and reduced precision., Conclusion: The CC population was not representative of the eligible population, introducing bias, in addition to worst precision. The 'missing-data modality method' results in biased estimates in non-randomized studies, as outcomes may be related to variables with missing values. Appropriate statistical methods for missing covariates, for example, MI, should therefore be considered., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: The GOG240 trial established bevacizumab with chemotherapy as standard first-line therapy for metastatic or recurrent cervical cancer. In the BEATcc trial (ENGOT-Cx10-GEICO 68-C-JGOG1084-GOG-3030), we aimed to evaluate the addition of an immune checkpoint inhibitor to this standard backbone., Methods: In this investigator-initiated, randomised, open-label, phase 3 trial, patients from 92 sites in Europe, Japan, and the USA with metastatic (stage IVB), persistent, or recurrent cervical cancer that was measurable, previously untreated, and not amenable to curative surgery or radiation were randomly assigned 1:1 to receive standard therapy (cisplatin 50 mg/m 2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m 2 , and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle) with or without atezolizumab 1200 mg. Treatment was continued until disease progression, unacceptable toxicity, patient withdrawal, or death. Stratification factors were previous concomitant chemoradiation (yes vs no), histology (squamous cell carcinoma vs adenocarcinoma including adenosquamous carcinoma), and platinum backbone (cisplatin vs carboplatin). Dual primary endpoints were investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumours version 1.1 and overall survival analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03556839, and is ongoing., Findings: Between Oct 8, 2018, and Aug 20, 2021, 410 of 519 patients assessed for eligibility were enrolled. Median progression-free survival was 13·7 months (95% CI 12·3-16·6) with atezolizumab and 10·4 months (9·7-11·7) with standard therapy (hazard ratio [HR]=0·62 [95% CI 0·49-0·78]; p<0·0001); at the interim overall survival analysis, median overall survival was 32·1 months (95% CI 25·3-36·8) versus 22·8 months (20·3-28·0), respectively (HR 0·68 [95% CI 0·52-0·88]; p=0·0046). Grade 3 or worse adverse events occurred in 79% of patients in the experimental group and in 75% of patients in the standard group. Grade 1-2 diarrhoea, arthralgia, pyrexia, and rash were increased with atezolizumab., Interpretation: Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression-free and overall survival and should be considered as a new first-line therapy option., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests AO reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de España, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Shattuck Labs, iTeos, and Eisai; travel and accommodation support from AstraZeneca, PharmaMar, and Roche; and funding paid to institution from AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology, Eisai, F Hoffmann-La Roche, Regeneron Pharmaceuticals, Immunogen, MSD de España, Takeda, PharmaMar, Tesaro, and Bristol Myers Squibb. LG reports support for attending meetings or travel from Viatris, GSK, and MSD; consulting fees paid to institution for participation in the advisory boards of Clovis, GSK, AstraZeneca, and Seagen; and speaker honoraria paid to institution from AstraZeneca, GSK, and Eisai. JM-G reports personal fees for participation in the advisory boards of AstraZeneca, Clovis, GSK, and PharmaMar; research grants paid to institution from GSK and Roche; and travel and accommodation expenses from GSK−Tesaro, Pfizer, and PharmaMar. GV reports honoraria for speaker engagements from MSD, Pierre Fabre, GSK, and Pfizer; and consulting fees from Reveal Genomics. UDG reports personal consulting fees from Amgen, AstraZeneca, Pfizer, BMS, Clovis Oncology, Dompé Farmaceutici, Merck, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Eisai, and Janssen; other funding paid to institution from AstraZeneca, Sanofi, and Roche; and support for attending meetings or travel from Pfizer, Ipsen, and AstraZeneca. KL reports personal honoraria from Eisai; participation on data safety monitoring or advisory boards of Eisai, MSD, Nykode, AstraZeneca, and GSK (honoraria paid to institution); and funding paid to institution from GSK. LW reports personal honoraria for participation in the advisory boards of AstraZeneca, Pfizer, GSK, Roche, MSD–Merck, Eisai, and Seagen; personal honoraria for speaker engagements from AstraZeneca, Eisai, GSK, Pfizer, Roche, MSD–Merck, and Seagen; and support for attending meetings or travel from GSK and MSD. NC reports consultancy or advisory roles for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD−Merck, Nuvation Bio, OncXerna, Pfizer, Pieris, and Roche; promotional speaker roles for AstraZeneca, Novartis, Clovis Oncology, MSD−Merck, and GSK; research grants from AstraZeneca, GSK, and Roche; and support for attending meetings or travel from AstraZeneca and GSK. LD reports personal fees for scientific advisory boards from Aadi Bioscience and Regeneron; fees paid to institution for scientific advisory boards from Merck; membership of the British Journal of Obstetrics and Gynaecology Editorial Board; personal royalties for writing expert content for UpToDate, Wiley, and the American Society of Clinical Oncology; personal fees for continuing medical education activities for Advance Medical, CEA Group, and Clinical Care Options; research funding paid to institution for investigator-initiated trials from Merck; clinical trial grants paid to institution from Genentech−Roche, AbbVie (GOG 3005), Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GSK–Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis; and fees paid to institution for membership of data and safety monitoring committees for Agenus and Inovio. AL reports personal fees for presentations or educational events from Medscape and PeerVoice; consulting fees paid to institution from Owkin; speaker honoraria paid to institution from MSD, GSK, AstraZeneca, and Eisai; fees paid to institution for participation in the advisory boards of AstraZeneca, MSD, Seagen, GSK, Genmab, Zentalis, and Blueprint; non-remunerated independent data safety monitoring board participation for Clovis and BMS; an educational grant paid to institution from AstraZeneca; and support for attending meetings or travel from OSE Immunotherapeutics. AG-O reports honoraria paid to institution for participation in the advisory board of Novartis; personal honoraria for speaker engagements from AstraZeneca, Pfizer, Novartis, and Lilly; and support for attending meetings or travel from Pfizer and Novartis. MJR reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD de España, Eisai, and Roche; personal fees for speaker engagements from MSD, AstraZeneca, Clovis Oncology, GSK, and PharmaMar; and travel and accommodation from AstraZeneca, PharmaMar, Roche, GSK, and MSD de España. LF-M reports honoraria paid to institution for participation in the advisory boards of GSK; honoraria paid to institution for speaker engagements from GSK, AstraZeneca–MSD, and Eisai; and support for attending meetings or travel from AstraZeneca–MSD and GSK. DL reports personal fees for participation in the advisory boards of AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Oncoinvent, PharmaMar, Seagen, and Sutro; personal fees for consultancy roles from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, PharmaMar, and Seagen; clinical trial or research funding to institution from Clovis Oncology, GSK, MSD, and PharmaMar; other financial or non-financial interests from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, Oncoinvent, PharmaMar, Roche, Seagen, and Sutro; and travel grants from AstraZeneca, Clovis Oncology, and GSK. IR-C reports personal honoraria for participation in the advisory boards of Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, Eisai, EQRx, GSK, Merck Serono, MacroGenics, Mersana, Novartis, Onxeo, Roche, and Sutro Biopharma; honoraria paid to institution for participation in the advisory boards of MSD (translational research); and funding paid to institution for translational research from BMS. LM reports participation in the advisory board of Roche; and honoraria for speaker engagements from Roche, GSK, Clovis Oncology, AstraZeneca, Pfizer, Novartis, and Lilly. FJ reports honoraria for lectures, expert boards, and educational events from AstraZeneca, Clovis Oncology, GSK, and Seagen; travel and accommodation support from GSK, Eisai, and MSD; and financial support for national academic GINECO trials from GSK and AstraZeneca. JA reports honoraria for speaker bureaus from GSK, Roche, AstraZeneca, MSD, PharmaMar, and Clovis; and advisory boards for GSK, MSD, AstraZeneca, and Clovis. PF reports personal fees for expert testimony from Daiichi; personal fees for invited speaker engagements from GSK and MSD; and support for attending meetings or travel from Lilly, Novartis, and GSK. IR reports personal fees for advisory boards from AstraZeneca, Clovis Oncology, GSK, PharmaMar, Roche, and MSD; and travel and accommodation from AstraZeneca, PharmaMar, Roche, and GSK. CL reports honoraria for advisory board participation from GSK; personal honoraria for speaker engagements from GSK, Clovis Oncology, Eisai, and MSD; and support for attending meetings or travel from MSD and GSK. JAP-F reports honoraria for speaker engagements from AstraZeneca, PharmaMar, Pharma&, Clovis, and GSK; payment for expert testimony from AstraZeneca, GSK, Roche, and PharmaMar; support for attending meetings or travel from Karyopharm, AstraZeneca, Roche, and PharmaMar; grants paid to institution from GSK and PharmaMar; equipment, materials, drugs, medical writing, gifts, or other services paid to institution from GSK; participation on data safety monitoring or advisory boards for Ability Pharma; and has a patent pending in breast cancer. HD reports personal honoraria for advisory board participation from AstraZeneca. LMR reports honoraria for speaker engagements from Genmab−Seagen, Blueprint Oncology, Curio Science, and Physicians Education Resource; honoraria for participation in the advisory boards of AstraZeneca, Clovis Oncology, GOG Foundation, Aadi Biosciences, Seagen, OnTarget Laboratories, Merck, Mersana, Rubius Therapeutics, Myriad Genetics, Genentech−Roche, Eisai, Novocure, and Immunogen; consulting fees from the GOG Foundation; and funding paid to institution from Genentech−Roche, On Target Laboratories, Pfizer, Aivita Biomedical, Tesaro, AstraZeneca, Merck, Akeso Biopharma, and Grupo Español de Investigación en Cáncer ginecologico. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. The performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity. Several challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application., (© 2024. The Author(s).)

Purposes: Lymphopenia is extensively studied, but not circulating leucocyte subpopulations, which however have distinct roles in tumor tolerance. Proton therapy has been shown to have a lesser impact on the immune system than conventional X-ray radiotherapy through lower dose exposure to healthy tissues. We explored the differential effects of brain X-ray and proton irradiation on circulating leucocyte subpopulations., Materials and Methods: Leucocyte subpopulation counts from tumor-free mice were obtained 12 hours after 4 fractions of 2.5 Gy. The relationships between irradiation type (X-rays or protons), irradiated volume (whole-brain/hemi-brain) and dose rate (1 or 2 Gy/min) with circulating leucocyte subpopulations (T-CD4+, T-CD8+, B, and NK-cells, neutrophils, and monocytes) were investigated using linear regression and tree-based modeling approaches. Relationships between dose maps (brain, vessels, lymph nodes (LNs)) and leucocyte subpopulations were analyzed and applied to construct the blood dose model, assessing the hypothesis of a direct lymphocyte-killing effect in radiation-induced lymphopenia., Results: Radiation-induced lymphopenia occurred after X-ray but not proton brain irradiation in lymphoid subpopulations (T-CD4+, T-CD8+, B, and NK-cells). There was an increase in neutrophil counts following protons but not X-rays. Monocytes remained unchanged under both X-rays and protons. Besides irradiation type, irradiated volume and dose rate had a significant impact on NK-cell, neutrophil and monocyte levels but not T-CD4+, T-CD8+, and B-cells. The dose to the blood had a heterogeneous impact on leucocyte subpopulations: neutrophil counts remained stable with increasing dose to the blood, while lymphocyte counts decreased with increasing dose (T-CD8+-cells > T-CD4+-cells > B-cells > NK-cells). Direct cell-killing effect of the dose to the blood mildly contributed to radiation-induced lymphopenia. LN exposure significantly contributed to lymphopenia and partially explained the distinct impact of irradiation type on circulating lymphocytes., Conclusions: Leucocyte subpopulations reacted differently to X-ray or proton brain irradiation. This difference could be partly explained by LN exposure to radiation dose. Further researches and analyses on other biological processes and interactions between leucocyte subpopulations are ongoing. The various mechanisms underlying leucocyte subpopulation changes under different irradiation modalities may have implications for the choice of radiotherapy modalities and their combination with immunotherapy in brain cancer treatment.

Aim: To synthesize a novel series of norfloxacin analogs and to evaluate biological activity. Methodology: Novel norfloxacin analogs were synthesized and characterized by NMR and mass spectrometry. Antiproliferative and antioxidant properties were studied. Results: Compound 2f was the most potent against HeLa cell-line with 100% inhibition of cell viability IC 50  = 3.1 ± 0.2 μM. All compounds exhibit moderate to excellent antioxidant properties. Docking study demonstrates higher binding affinity of compounds with respective anticancer (B-cell lymphoma-2) and (tyrosinase) antioxidant targets. In silico absorption, distribution, metabolism and excretion profile of compounds proves all synthesized compounds follow Lipinski's rule of drug likeness, non toxic and possess passive gastrointestinal absorption. Conclusion: The biological profile suggest that the synthesized norfloxacin analogs can be a novel scaffold for future anticancer drug development.

Purpose: The discovery of X-rays was followed by a variety of attempts to treat infectious diseases and various other non-cancer diseases with ionizing radiation, in addition to cancer. There has been a recent resurgence of interest in the use of such radiotherapy for non-cancer diseases. Non-cancer diseases for which use of radiotherapy has currently been proposed include refractory ventricular tachycardia, neurodegenerative diseases (e.g. Alzheimer's disease and dementia), and Coronavirus Disease 2019 (COVID-19) pneumonia, all with ongoing clinical studies that deliver radiation doses of 0.5-25 Gy in a single fraction or in multiple daily fractions. In addition to such non-cancer effects, historical indications predominantly used in some countries (e.g. Germany) include osteoarthritis and degenerative diseases of the bones and joints. This narrative review gives an overview of the biological rationale and ongoing preclinical and clinical studies for radiotherapy proposed for various non-cancer diseases, discusses the plausibility of the proposed biological rationale, and considers the long-term radiation risks of cancer and non-cancer diseases., Conclusions: A growing body of evidence has suggested that radiation represents a double-edged sword, not only for cancer, but also for non-cancer diseases. At present, clinical evidence has shown some beneficial effects of radiotherapy for ventricular tachycardia, but there is little or no such evidence of radiotherapy for other newly proposed non-cancer diseases (e.g. Alzheimer's disease, COVID-19 pneumonia). Patients with ventricular tachycardia and COVID-19 pneumonia have thus far been treated with radiotherapy when they are an urgent life threat with no efficient alternative treatment, but some survivors may encounter a paradoxical situation where patients were rescued by radiotherapy but then get harmed by radiotherapy. Further studies are needed to justify the clinical use of radiotherapy for non-cancer diseases, and optimize dose to diseased tissue while minimizing dose to healthy tissue.

Aim: To describe first-line treatment patterns, overall survival (OS) and real-world progression-free survival (rwPFS) in young women (<40) with metastatic breast cancer (mBC), as compared to women aged 40-69., Materials and Methods: Data on adult women diagnosed with mBC (2008-2017) were extracted from the ESME mBC database (NCT03275311) which includes consecutive patients starting first-line metastatic treatment in one of the 18 French Comprehensive cancer centers. We reported first-line therapeutic strategy and prognostic factors of OS and rwPFS for women aged < 40 and 40-69., Results: In total, 14,897 mBC women were included (1512 aged <40). HR+ /HER2- mBC was the most frequent subtype. First-line treatment differed between young patients and older ones for HR+ /HER2- and Triple Negative (TN) mBC. Median OS for women aged < 40 and 40-69, respectively, was 46.9 and 46.2 months for HR+ /HER2- mBC; 13.5 and 15.2 for TN mBC; and, 60.7 and 55.1 for HER2 + mBC. Median rwPFS under first line treatment was 11.6 and 11.9 months for HR+ /HER2- in women aged < 40 and 40-69, respectively; 5.5 and 5.9 for TN, and, 13.3 and 12.9 for HER2 + . Factors associated with shorter OS and rwPFS were similar for both women aged < 40 and 40-69 and included ≥ 3 metastatic sites, visceral metastases, and longer MFI, with time-varying effects observed for several prognostic factors., Conclusion: Young women presented more frequently with TN and HER2 + subtypes and aggressive mBC than women aged 40-69 did. Prognostic factors of OS and rwPFS were quite similar between age groups and mBC subtypes., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: In order to tackle social inequalities in mortality, it is crucial to quantify them. We produced French deprivation-specific life tables for the period 2016-2018 to measure the social gradient in adult all-cause mortality., Methods: Data from the Permanent Demographic Sample (EDP) were used to provide population and death counts by age, sex and deprivation quintile. The European Deprivation Index (EDI), applied at a sub-municipal geographical level, was used as an ecological measure of deprivation. Smoothed mortality rates were calculated using a one-dimensional Poisson counts smoothing method with P-Splines. We calculated life expectancies by age, sex and deprivation quintile as well as interquartile mortality rate ratios (MRR)., Results: At the age of 30, the difference in life expectancy between the most and least deprived groups amounted to 3.9 years in males and 2.2 years in females. In terms of relative mortality inequalities, the largest gaps between extreme deprivation groups were around age 55 for males (MRR = 2.22 [2.0; 2.46] at age 55), around age 50 in females (MRR = 1.77 [1.48; 2.1] at age 47), and there was a decrease or disappearance of the gaps in the very older adults., Conclusions: There is a strong social gradient in all-cause mortality in France for males and females. The methodology for building these deprivation-specific life tables is reproducible and could be used to monitor its development. The tables produced should contribute to improving studies on net survival inequalities for specific diseases by taking into account the pre-existing social gradient in all-cause mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Merville, Rollet, Dejardin, Launay, Guillaume and Launoy.)

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy., (© 2023. The Author(s).)

Background: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort., Methods: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success., Results: From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%-[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%-[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%)., Conclusion: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown., Methods: In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR)., Results: 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death., Conclusion: HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DM: Consulting/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Bionest Partners, BMS, Incyte, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Simon-Kutcher & Partners, Servier, Taiho. Honoraria for lectures: Amgen, AstraZeneca, Bayer, BMS, Foundation Medicine, Incyte, Leo Pharma, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier, Veracyte, Viatris. Personal fees for a writing engagement: Medscape. Travel expenses for medical congresses: Amgen, Bayer, BMS, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier, Viatris. BV: none. MF: honoraria for lectures: Novartis. Travel expenses for medical congresses: Ipsen. RG: Consulting/advisory role: Pierre Fabre, BMS, Servier, MSD. Honoraria for lectures: MSD, Servier, Ipsen, BMS, Viatris. Travel expenses for medical congresses: MSD, Ipsen, Roche, Pierre Fabre, Advanced Accelerator Applications (AAA). CC: none. JE: Consulting/advisory role: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene. Travel expenses for medical congresses: Amgen. Research funding (institutional): BMS, Beigene. MPG: honoraria: Servier, BMS. Travel expenses for medical congresses: AAA, Bayer, Servier, Amgen. LBG: honoraria: AstraZeneca, Servier, KSK, MSD, Bayer, Eisai. DS: travel expenses for medical congresses: Servier, Pierre Fabre. EDB: none. TDB: Consulting/advisory role: Terumo, Boston Scientific. Research funding (institutional): Quantum, Terumo. DG: honoraria for lectures: Merck Serono, Amgen, Sanofi, Servier. PD: Consulting/advisory role: MSD. Honoraria for lectures: AstraZeneca, MSD. Travel expenses for medical congresses: MSD. LL: none. VB: Consulting/advisory role: Merck Serono, Ipsen, Bayer, Eisai, BMS, Roche, AstraZeneca. Honoraria for lectures: Merck Serono, Novartis, Roche, Bayer, MSD, Amgen, Ipsen, AstraZeneca. Travel expenses for medical congresses: Amgen, Merck Serono, Sanofi Genzyme, Bayer, Roche, MSD, Ipsen, AstraZeneca. Research funding (institutional): Merck Serono. MG: none. JPP: none. MD: honoraria for advisory boards or as a presenter in symposium: Merck Serono, MSD, Amgen, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, Lilly, Sanofi, Servier, Daiichi Sankyo., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The last year of the radiotherapy oncology internship in France has become a phase of empowerment, called "junior doctor", allowing interns to validate acts previously reserved only for senior doctors. This study focused on the responsibilities given to the first promotion of junior doctors in France and their feelings on this new status., Material and Methods: A cross-sectional survey was carried out by the French associations of interns and young doctors in oncology, Aerio and SFjRO. A questionnaire was sent to the class referents of each city for transmission to the junior doctors of the year 2021-2022 from September 1st to November 30th, 2022. The questions concerned training, the modalities of this year and the feelings. Responses were analyzed anonymously using R. 4.3.1 software., Results: For radiation oncology, 33 responses were obtained from 21 cities. For most junior doctors, three to four localizations (51%) were performed with an average of five new patients per week. The contours were reviewed either systematically (51%) or only at the beginning (32%). Dosimetry was reported as never countersigned in 19%; 80% of junior doctors described having been the only radiation oncologist during multidisciplinary staff meetings. The two main areas of improvement were theoretical training (45%) and legal frameworks/contracts (42%)., Conclusion: These results relating to the first class of junior doctors showed an overall agreement with the recommendations of the Cnec. Feedback from interns was positive. The supervision of brachytherapy and dosimetry activities, the presence alone in multidisciplinary panel remained points of vigilance., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)