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[...]in light of the potential for patients with cancer to be infected with SARS-CoV-2 during this pandemic treatment decision making should take into account cancer type, disease extent, prognosis, and treatment opportunities irrespective of a patient's age, but acknowledge the excess risks associated with viral infection in older patients. [...]evaluation of life expectancy should be part of treatment decision making. [...]as much as possible, alternatives to standard therapy that have few side-effects on the immune system (eg, endocrine therapy vs chemotherapy) should be favoured, and are preferred to no treatment, which might lead ultimately, long after the epidemic, to excess cancer-related deaths.

Circulating tumor DNA (ctDNA) analysis offers a non-invasive approach to molecular profiling. While RAS mutations are well-established predictive biomarkers in metastatic colorectal cancer (mCRC), the prognostic value of their variant allele frequency (VAF) remains unclear. We retrospectively analyzed individual patient data with mCRC who underwent ctDNA testing using the FoundationOne® Liquid CDx assay. The primary objective was to determine the optimal RAS VAF cutoff for overall survival (OS) prognostication. Between November 2020 and July 2024, 282 patients were enrolled. Among 265 eligible patients, 134 (50.6%) were ctRAS mutant, 25 (9.4%) ctBRAFV600E mutant, and 106 (40.0%) were ctRAS/BRAF wild-type. A RAS VAF threshold of 5% yielded the highest prognostic discrimination for OS (HR = 2.41; 95% CI 1.65–3.55; p < 0.0001; C-index = 0.601). ctRAS-high mutant tumors (VAF ≥ 5%) were associated with synchronous metastatic disease, multiple metastatic sites, higher blood tumor mutational burden, and elevated tumor fraction. ctRAS-low mutant tumors (VAF < 5%) were more frequently metachronous, presented with a single metastatic site, and showed liver involvement. High RAS VAF in ctDNA is a strong and independent prognostic marker for OS in mCRC. Quantitative ctDNA profiling may enhance risk stratification and guide personalized management strategies.

Background Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel. Methods Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months. Results Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia. Conclusion Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m 2 , median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified. Study registration It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu , as EUPAS10391. It has been approved as an ENCEPP SEAL study.

Background We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations. Methods PUBMED database was searched in October 2021 for articles published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines. Results Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80–85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case. Conclusion The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75–80 age group. IRB An institutional review board composed of members of the 2 learned societies (SOFOG and FFCD) defined the issues of interest, followed the evolution of the work and reviewed and validated the report.

Background Atresia of the infrarenal inferior vena cava (IVC) is associated with thrombophilia and antithrombin (AT) deficiency (ATD) due to homozygosity for the so-called Budapest 3 variant, c.391C > T, in the gene, SERPINC1 . Case presentation We report on a father and his two sons that had severe thrombosis at a young age. One son had absence of, and the other had very gracile infrarenal IVC. The father had gracile vena iliaca. All had significant collateral building. AT activity was determined with four different methods and varied between moderately reduced and borderline normal values, depending on the method. While all were heterozygous for c.391C > T, the father was also heterozygous for a variant of uncertain significance in SERPINC1 . Conclusions The findings support the association between c.391C > T in SERPINC1 , thrombophilia, and atresia of the IVC system and indicate that even heterozygosity for c.391C > T may contribute to such anomalies. ATD detection was hampered by the varying sensitivity of methods used for AT activity measurement.

Background/Objectives: The prognostic significance of blood tumor mutational burden (bTMB) in metastatic colorectal cancer (mCRC) remains poorly defined. While tissue-based TMB has been associated with favorable outcomes in selected colorectal cancer subgroups, the clinical meaning of bTMB in real-world practice is unclear. This study evaluated the prognostic impact of bTMB measured through liquid biopsy in an unselected cohort of patients with mCRC. Methods: This monocentric, real-world study included 255 adult patients with pMMR/MSS mCRC who underwent routine comprehensive genomic profiling using the FoundationOne® Liquid CDx assay. bTMB was quantified in mutations per megabase (mut/Mb), and patients were classified into bTMB-low and bTMB-high groups using the cohort median. The primary endpoint was overall survival (OS). Subgroup analyses, including stratification by RAS/BRAF mutation status, were descriptive. Results: The median bTMB was 5 mut/Mb. Patients in the bTMB-high group had an increased risk of death compared with those in the bTMB-low group (hazard ratio (HR) 1.88). The adverse prognostic effect for OS of high bTMB was more pronounced in patients with RAS mutant tumors (HR 2.32) than with RAS/BRAF wild-type tumors (HR 1.81), while no prognostic impact was observed in BRAFV600E mutant tumors (HR 0.90). bTMB was strongly correlated with ctDNA fraction (p < 0.0001). Conclusions: In routine clinical practice, elevated bTMB is associated with poor prognosis in pMMR/MSS mCRC, particularly in RAS mutant tumors. These results contrast with prior tissue-based studies and indicate that bTMB may reflect tumor burden and aggressive disease biology rather than tumor immunogenicity. Prospective studies integrating bTMB with ctDNA fraction, tumor burden metrics, and longitudinal molecular dynamics are warranted to refine its clinical utility.

BackgroundCancer management in the elderly is often considered as suboptimal, highly variable, and rarely evidence-based. Data are needed to understand decision-making processes in this population.Materials and methodsA survey was performed in France to describe decision-making in gynaecologic patients over 70. It followed a three-step method: (1) 101 representative physicians questioned about treatment decision criteria; (2) simplified individual data were collected; (3) as well as detailed data patients receiving chemotherapy. This analysis refers to breast cancer subgroup of patients.ResultsMain decision criteria were performance status, comorbidities, and renal function. In adjuvant setting, the main concern was life expectancy, whereas it was quality of life in metastatic setting. Of the 631 patients entered in the simplified analysis, 41% had been evaluated by a geriatrician, 67% received chemotherapy. In the detailed analysis, patients older than 75 were more likely to receive a monochemotherapy and to be treated with weekly/divided dose. In adjuvant setting, respectively, 19, 55, and 26% of the patients were treated with regimen validated in the elderly, validated in a younger population, and not validated. A G-CSF was prescribed in 48% of the patients, as primary prophylaxis in 78 and in 41% of patients with a risk of febrile neutropenia < 10%.ConclusionGeriatric covariates become an increasing concern in the decision-making process. This survey also suggests an insufficient use of validated chemotherapy regimens. To date, age remains a risk factor for heterogeneity in oncologic practice justifying a persistent effort for elaborating and disclosing specific recommendations.

PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p<0·001). Patients with a SPECTRA Score >0·02 had a lower OS in the training cohort (p<0·0001), in the validation cohort (p<0·0008) and in the external validation cohort (p=0·0027). SPECTRA Score at 2 months had the same prognostic value as RECIST at 6 months, while non-response according to RECIST1·1 at 2 months was not associated with a lower OS in the validation cohort (p=0·238). Morphological response was not associated with OS (p=0·41).ConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.

Background/Objectives: Cancer progression and the hemostatic system are closely linked. Coagulation factor V (FV) has a key function in coagulation, with both pro- and anticoagulant functions. FV gene (F5) expression and F5 variants have been linked to breast cancer progression. The direct impact of F5 variants on FV expression and functional effects in breast cancer are unknown. We aimed to investigate whether the F5 variants FV Leiden (F5 rs6025) and F5 rs6028 influenced FV expression, coagulant activity, and apoptosis in breast cancer cells. Methods: MDA-MB-231 cells were transfected with overexpression plasmids containing F5 wild type, F5 rs6025 or F5 rs6028. We investigated the functional impact of the F5 variants on F5 mRNA, FV protein, FV coagulant activity, and apoptosis in vitro, and examined the potential of the variants as transcriptional regulators of F5 expression in silico. Results: Increased F5 mRNA, FV protein, and apoptosis were observed in cells transfected with F5 wild-type overexpression plasmid compared to empty vector. F5 mRNA, protein, coagulant activity, and apoptosis were further increased with the F5 rs6025 and F5 rs6028 variants compared to F5 wild type. Cis-expression quantitative trait loci analyses indicated a regulatory effect of F5 rs6028, and putative transcription factor binding sites for several transcription factors overlapped with the position of F5 rs6025. Conclusions: Our study demonstrated that F5 rs6025 and F5 rs6028 have a regulatory effect on FV synthesis that might affect apoptosis in breast cancer. The F5 variants might therefore enhance the tumor suppressor function of FV in breast cancer.

We have done a systematic literature review about CRC Screening over 75 years old in order to update knowledge and make recommendations. PUBMED database was searched in October 2021 for articles published on CRC screening in the elderly, and generated 249 articles. Further searches were made to find articles on the acceptability, efficacy, and harms of screening in this population, together with the state of international guidelines. Most benefit-risk data on CRC screening in the over 75 s derived from simulation studies. Most guidelines recommend stopping cancer screening at the age of 75. In private health systems, extension of screening up to 80-85 years is, based on the life expectancy and the history of screening. Screening remains effective in populations without comorbidity given their better life-expectancy. Serious adverse events of colonoscopy increase with age and can outweigh the benefit of screening. The great majority of reviews concluded that screening between 75 and 85 years must be decided case by case. The current literature does not allow Evidence-Based Medicine propositions for mass screening above 75 years old. As some subjects over 75 years may benefit from CRC screening, we discussed ways to introduce CRC screening in France in the 75-80 age group.