Cost-effectiveness of CTC guided chemo- or endocrine therapy in ER+ HER2- metastatic breast cancer – results from a randomized controlled multicenter trial

Patients with metastatic, Estrogen Receptor (ER) positive, HER2-negative, breast cancer, before initiating CDK4/6 inhibitors, receive either single agent endocrine- or chemotherapy based on their clinical risk. In this first-ever trial-based economic evaluation of Circulating Tumor Cells (CTCs), the cost-effectiveness of standardizing the prescription of endocrine- or chemotherapy using a CTC count threshold (with >5 CTCs/7.5mL indicative of unfavorable disease outcomes) was compared to current clinical practice. N=755 ER+ HER2-patients, enrolled in 17 French centres, were randomized to CTC guided or standard of care and were treated according to either through the CTC score or clinical examination. Health state utilities were calculated by mapping the QLQ-C30 to EQ-5D utilities and used to calculate Quality-Adjusted Life Years (QALY) over a 2-year time horizon. Bootstrapping and additional sensitivity analyses were performed to quantify the impact of uncertainty. Health outcomes in both arms were similar, but costs were higher in the CTC guided arm (€19,403) compared to the usual care (€18,254), resulting in an ICER of €104,078/QALY in favor of usual care. However, when the analysis was performed for the clinically high- and low-risk groups separately, CTC enumeration could be a dominant strategy (cost saving) if treatment is de-escalated in clinically high-risk patients as indicated by CTC scores. However, the current analysis was based on the PFS and OS data reported in 2021 and long-term Overall Survival data is collected since then (JCO, 2023 in press). A further analysis of the health economic impact of CTC enumeration in clinically low and high-risk groups is therefore indicated

Circulating Tumor Cells: Finding Rare Events for A Huge Knowledge of Cancer Dissemination

The analysis of circulating tumor cells (CTCs) as a real-time liquid biopsy approach can be used to obtain new insights into metastasis biology, and as companion diagnostics to improve the stratification of therapies and to obtain insights into the therapy-induced selection of cancer cells. In this book, we will cover all the different facets of CTCs to assemble a huge corpus of knowledge on cancer dissemination: technologies for their enrichment, detection, and characterization; their analysis at the single-cell level; their journey as CTC microemboli; their clinical relevance; their biology with the epithelial-to-mesenchymal transition (EMT); their stem-cell properties; their potential to initiate metastasis at distant sites; their ex vivo expansion; and their escape from the immune system

Pertinence clinique de la maladie micrometastatique prostatique (résultats de l'étude pilote EPISTOT-PSA)

Contexte: La prise en charge du cancer de la prostate est imparfaite et de nouveaux outils sont nécessaires à toutes les étapes de la maladie: dépistage, stadification, pronostic. Ce travail propose d'étudier la technique EPISPOT-PSA de détection des cellules tumorales circulantes dans le cadre du cancer de la prostate localisé après une revue de littérature de l'épidémiologie du cancer de la prostate, de ses difficultés de prise en charge, et de la maladie micrométastatique avec les méthodes de sa mise en évidence. Matériel et méthodes : 178 patients ont bénéficié d'une évaluation prostatique entre 2002 et 2006 par biopsie et test EPISPOT-PSA. Une analyse rétrospective des dossiers a permis d'extraire les données requises pour l'identification des cancers localisés et des sujets témoins. Résultats:111 patients étaient disponibles pour analyse, dont 48 avaient un cancer diagnostiqué immédiatement après le test EPISPOT-PSA, 10 secondairement et 53 restaient sains pendant la période de suivi. Le test EPISPOT-PSA était associé au diagnostic de cancer en analyse univariée (p=0,005) mais pas en analyse multivariée, contrairement au PSA total (p=O,OOl), au volume prostatique (p=0,018), à l'âge (p=0,019) et au nombre de séries de biopsies (p<O,OOl). L'aire sous la courbe ROC de sa prédiction du résultat de la biopsie était de 0,646, statistiquement différente du hasard mais pas du PSA. Chez les patients pris en charge pour cancer, un test positif était statistiquement associé à une moindre survie spécifique (p=0,045) et il existait une tendance similaire pour la survie globale (p=0,076). Conclusion: Les caractéristiques du test n'autorisaient pas son utilisation dans le cadre du dépistage, ni de la stadification. Il posséderait par contre une valeur prédictive de la survie spécifique, à confirmer par une analyse prospective.Overview: Prostate cancer handling needs improvement concerning screening, staging and prognosis. Herein we discuss those limits, as well as its epidemiology. We review carcinogenesis, minmal residual disease and its detection issues. Finally EPISPOT-PSA assay is evaluated through a pilot study. Material and methods One hundread seventy eight patients underwent prostatic evaluation by trans-rectal ultrasound guided biopsies and EPISPOT-PSA assay from 2002 to 2006. Their files were retrospectively reviewed in order to gather c1inical data and compare cancer diagnosed patients and controls. Results : One hundread and eleven patients were included, ofwhich 48 were im'l'Iediately cancer diagnosed, 10 were secondary cancer diagnosed and 53 never presented any evidence of cancer. There was a statistically significant link between cancer diagnosis and EPIS POT -PSA assay result (p=0,005) but it was dependant to PSA. Total PSA (p=O,OOl), prostate volume (=0,018), age (p=0,019) and number ofbiopsy sessions (p<O,OOl) were independently linked to cancer diagnosis. Area under the Receiver Operating Charecteristic curve was 0,646, that was different from 0,5 but not from total PSA AUC. Wh en restricting analyses to the immediately cancer diagnosed patients, a positive EPISPOT-PSA assay was inversely associated with overall survival (trend, p=0.076), et specific survival (p=0,045). Conclusion EPISPOT-PSA assay's characteristics were not relevant concerning neither screening nor staging. It could help predicting specific survivai. Thus, further prospective study is required.MONTPELLIER-BU Médecine UPM (341722108) / SudocSudocFranceF

Photonic Technologies for Liquid Biopsies: Recent Advances and Open Research Challenges

Dell'Olio F, Su J, Huser T, Sottile V, Cortes-Hernandez LE, Alix-Panabieres C. Photonic Technologies for Liquid Biopsies: Recent Advances and Open Research Challenges. Laser &amp; Photonics Reviews. 2020;15(1): 2000255.The recent development of sophisticated techniques capable of detecting extremely low concentrations of circulating tumor biomarkers in accessible body fluids, such as blood or urine, could contribute to a paradigm shift in cancer diagnosis and treatment. By applying such techniques, clinicians can carry out liquid biopsies, providing information on tumor presence, evolution, and response to therapy. The implementation of biosensing platforms for liquid biopsies is particularly complex because this application domain demands high selectivity/specificity and challenging limit-of-detection (LoD) values. The interest in photonics as an enabling technology for liquid biopsies is growing owing to the well-known advantages of photonic biosensors over competing technologies in terms of compactness, immunity to external disturbance, and ultrahigh spatial resolution. Some encouraging experimental results in the field of photonic devices and systems for liquid biopsy have already been achieved by using fluorescent labels and label-free techniques and by exploiting super-resolution microscopy, surface plasmon resonance, surface-enhanced Raman scattering, and whispering gallery mode resonators. The current state-of-the-art is critically reviewed here, starting from the requirements imposed by the detection of the most common circulating biomarkers. Open research challenges are considered together with competing technologies, and the most promising paths of improvement are discussed for future applications

On the need for integrating cancer into the One Health perspective

International audienceRecent pandemics have highlighted the urgency to connect disciplines studying animal, human, and environment health, that is, the “One Health” concept. The One Health approach takes a holistic view of health, but it has largely focused on zoonotic diseases while not addressing oncogenic processes. We argue that cancers should be an additional key focus in the One Health approach based on three factors that add to the well-documented impact of humans on the natural environment and its implications on cancer emergence. First, human activities are oncogenic to other animals, exacerbating the dynamics of oncogenesis, causing immunosuppressive disorders in wildlife with effects on host–pathogen interactions, and eventually facilitating pathogen spillovers. Second, the emergence of transmissible cancers in animal species (including humans) has the potential to accelerate biodiversity loss across ecosystems and to become pandemic. It is crucial to understand why, how, and when transmissible cancers emerge and spread. Third, translating knowledge of tumor suppressor mechanisms found across the Animal Kingdom to human health offers novel insights into cancer prevention and treatment strategie

Demographic Analysis of Cancer Research Priorities and Treatment Correlations

Understanding the diversity in cancer research priorities and the correlations among different treatment modalities is essential to address the evolving landscape of oncology. This study, conducted in collaboration with the European Cancer Patient Coalition (ECPC) and Childhood Cancer International-Europe (CCI-E) as part of the “UNCAN.eu” initiative, analyzed data from a comprehensive survey to explore the complex interplay of demographics, time since cancer diagnosis, and types of treatments received. Demographic analysis revealed intriguing trends, highlighting the importance of tailoring cancer research efforts to specific age groups and genders. Individuals aged 45–69 exhibited highly aligned research priorities, emphasizing the need to address the unique concerns of middle-aged and older populations. In contrast, patients over 70 years demonstrated a divergence in research priorities, underscoring the importance of recognising the distinct needs of older individuals in cancer research. The analysis of correlations among different types of cancer treatments underscored the multidisciplinary approach to cancer care, with surgery, radiotherapy, chemotherapy, precision therapy, and biological therapies playing integral roles. These findings support the need for personalized and combined treatment strategies to achieve optimal outcomes. In conclusion, this study provides valuable insights into the complexity of cancer research priorities and treatment correlations in a European context. It emphasizes the importance of a multifaceted, patient-centred approach to cancer research and treatment, highlighting the need for ongoing support, adaptation, and collaboration to address the ever-changing landscape of oncology

Aligning Cancer Research Priorities in Europe with Recommendations for Conquering Cancer: A Comprehensive Analysis

International audienceImprovements in cancer care require a new degree of collaboration beyond the purely medical sphere, extending deeply into the world of other stakeholders—preeminently patients but also the other stakeholders in the hardware and software of care. Cancer remains a global health challenge, necessitating collaborative efforts to understand, prevent, and treat this complex disease. To achieve this goal, a comprehensive analysis was conducted, aligning the prioritization of cancer research measures in 13 European countries with 13 key recommendations for conquering cancer in the region. The study utilized a survey involving both patients and citizens, alongside data from IQVIA, a global healthcare data provider, to assess the availability and access to single-biomarker tests in multiple European countries. The results revealed a focused approach toward understanding, preventing, and treating cancer, with each country emphasizing specific research measures tailored to its strengths and healthcare objectives. This analysis highlights the intricate relationship between research priorities, access to biomarker tests, and financial support. Timely access to tests and increased availability positively influence research areas such as cancer prevention, early detection, ageing, and data utilization. The alignment of these country-specific measures with 13 recommendations for conquering cancer in Europe underscores the importance of tailored strategies for understanding, preventing, and treating cancer

Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity

Functional studies giving insight into the biology of circulating tumor cells (CTCs) remain scarce due to the low frequency ofCTCs and lack of appropriate models. Here, we describe the characterization of a novelCTC-derived breast cancer cell line, designatedCTC-ITB-01, established from a patient with metastatic estrogen receptor-positive (ER+) breast cancer, resistant to endocrine therapy.CTC-ITB-01 remainedER(+)in culture, and copy number alteration (CNA) profiling showed high concordance betweenCTC-ITB-01 andCTCs originally present in the patient with cancer at the time point of blood draw.RNA-sequencing data indicate thatCTC-ITB-01 has a predominantly epithelial expression signature. Primary tumor and metastasis formation in an intraductalPDXmouse model mirrored the clinical progression ofER(+)breast cancer. DownstreamERsignaling was constitutively active inCTC-ITB-01 independent of ligand availability, and theCDK4/6 inhibitor Palbociclib strongly inhibitedCTC-ITB-01 growth. Thus, we established a functional model that opens a new avenue to studyCTCbiology