Cost-Utility Analysis of Continuation Versus Discontinuation of First-Line Chemotherapy in Patients With Metastatic Squamous-Cell Esophageal Cancer: Economic Evaluation Alongside the E-DIS Trial.

OBJECTIVES: Continuous chemotherapy has been used to treat patients with metastatic esophageal squamous cell carcinoma (mESCC), despite weak evidence supporting a clinical benefit, associated side effects for the patients, and unjustified medical costs. In the French setting, we conducted a cost-utility analysis alongside the randomized E-DIS trial (NCT01248299), which compared first-line fluorouracil/platinum-based chemotherapy continuation (CT-CONT) to CT discontinuation (CT-DISC) in progressive-free patients after an initial 6-week treatment phase. METHODS: A partitioned survival analysis was performed using patient-level data collected during the trial for survival outcomes, quality of life (EQ-5D-3L), and medical costs. The mean quality-adjusted life-years (QALYs) and medical costs were estimated over an 18-month period to assess the incremental net monetary benefit and incremental cost-effectiveness ratio. Uncertainty was handled using the nonparametric bootstrap and univariate analysis. Sixty-seven patients with mESCC were randomized and included in the cost-utility analysis. RESULTS: On average, CT-CONT slightly decreased the number of QALYs (-0.038) and increased the cost per patient (+ €1177). At a willingness-to-pay threshold of €50 000/QALY, the incremental net monetary benefit was negative (-€3077 [95% confidence interval: -6564; 4359]), and the incremental cost-effectiveness ratio was -30 958€/QALY (CT-CONT dominated). The probability of the CT-CONT treatment option being cost-effective at a willingness-to-pay threshold of €50 000/QALY, compared to CT-DISC, was 29%. CONCLUSIONS: CT-DISC may be considered as an alternative therapeutic option to CT-CONT in patients with mESCC who have stable disease after an initial chemotherapy treatment phase. A continuous chemotherapy could indeed reduce the number of QALYs because of the disutility associated with the continuous treatment.

Clinical Outcomes in Ring Avulsion Fingers and Systematic Review of the Literature.

Ring avulsions continue to be a challenge in reconstructive surgery. We conducted a retrospective study and reviewed all Urbaniak-Kay type IV degloving injuries replanted at our institution between 2011 and 2018. A systematic review of the literature was also conducted to assess the survival rates, functional, and sensibility outcomes. The results of our systematic review outline a survival rate of 79.50% (101/127). With 1 artery being repaired, 79% of the fingers survived, a value that increased to 87.50% when 2 arteries were anastomosed (P = 0.484). Statistically significant differences (P < 0.001) were found when comparing the survival rates of the fingers with 2 or more veins repaired (87%) with those with only 1 vein anastomosed (51.90%). In terms of nerve reconstruction, there was a significant difference (P < 0.001) with the 2-point discrimination test in favor of the reconstructed group when nerve reparation was done (10.80 mm ± 2.95 mm) versus when digital nerves were not repaired (15.25 mm ± 0.50 mm). Fingers after secondary procedures did not obtain better mobility. The mean total active motion in nonreoperated fingers was 221 degrees (195-270 degrees), whereas the total active motion in the cases who received secondary surgeries was 152 degrees (110-195 degrees), with statistically significant differences (P = 0.02). Therefore, we recommend attempting replantation of degloved fingers. All efforts must be done to carry out 2 vein anastomoses, and our results strongly recommend attempting at least some kind of nerve reconstruction. Secondary surgeries should be reserved for selected cases only, because of the extensive scarring in this kind of injuries. Early mobilization protocols must be encouraged to achieve a good functional result.

The cost of molecular-guided therapy in oncology: a prospective cost study alongside the MOSCATO trial.

AIM: There is increasing use of molecular technologies to guide cancer treatments, but few cost data are available. Our objective was to assess the costs of molecular-guided therapy for patients with advanced solid tumors alongside the Molecular Screening for Cancer Treatment and Optimization (MOSCATO) trial. MATERIALS AND METHODS: The study population consisted of 529 patients. The molecular diagnosis included seven steps from tumor biopsy to the multidisciplinary molecular tumor board. The cost of a complete molecular diagnosis was assessed by micro-costing. Direct costs incurred from enrollment until progression were assessed from the French National Health Insurance perspective. RESULTS: The patients' mean age was 54 years (range: 3-82) and the mean follow-up period was 145 days (range: 1-707 days). A complete molecular diagnosis cost [euro ]2,396. There were 220 patients with an actionable target (42%), among whom 105 (20%) actually received a targeted therapy. The cost of molecular-guided therapy per patient was [euro ]31,269. The main cost drivers were anticancer drugs (54%) and hospitalizations (35%). CONCLUSION: This prospective cost analysis showed that molecular diagnosis accounts for only 6% of the cost of molecular-guided therapy per patient. The costs of drugs and hospitalizations are the main cost drivers.Genet Med advance online publication 01 December 2016.

A prospective multicenter study on bladder cancer: the COBLAnCE cohort.

BACKGROUND: Bladder cancer is a very heterogeneous disease as regards natural history. Environmental exposures, constitutional genetic and/or epigenetic background may affect not only the likelihood of bladder tumor occurrence, but also the histologic type of cancer and its outcome. Currently, only a few data are available to study the prognostic role of genetic and environmental factors. Likewise, data on the economic burden of bladder cancer and the longitudinal impact of the disease and the treatments on patient quality of life are scarce. METHODS: COBLAnCE is a large French-based clinical cohort study on bladder cancer. Newly diagnosed patients are enrolled prospectively in 12 public hospitals and 5 private for profits hospitals. The target sample size is 2,000 patients. All patients are to be followed for 6 years. Information on patient characteristics and lifestyle is collected during a face-to-face interview at enrollment. Clinical information on disease presentation, diagnosis, and treatment is extracted from medical records for the primary tumor and for all subsequent local and distant recurrences. Quality of life and resource use is collected at recruitment and during follow-up. In parallel, 4 types of biological samples (blood, tumor tissue, urine and nail) are collected, at baseline and during follow-up. DNA, RNA and PBMLs are extracted from blood samples, DNA and RNA from stabilized urine, proteins from frozen urine, DNA, RNA and proteins from frozen tumor tissues, and DNA and RNA from formalin-fixed paraffin-embedded tumor tissues. All derived products are stored at -80 °C or in liquid nitrogen. Main endpoints are gene-environment interactions, molecular classification, biomarker discovery, therapeutic innovation, treatment patterns, healthcare resource use, bladder cancer outcomes and quality of life. DISCUSSION: The COBLAnCE cohort will provide considerable insight into the biology of bladder cancer and the mechanisms through which genetic and environmental factors may influence the prognosis. It may allow the discovery of emerging biomarkers. Finally, economic data will be useful for future cost-effectiveness studies of immunotherapy drugs or other therapeutics in bladder cancer.

Bias and precision of methods for estimating the difference in restricted mean survival time from an individual patient data meta-analysis.

BACKGROUND: The difference in restricted mean survival time ([Formula: see text]), the area between two survival curves up to time horizon [Formula: see text], is often used in cost-effectiveness analyses to estimate the treatment effect in randomized controlled trials. A challenge in individual patient data (IPD) meta-analyses is to account for the trial effect. We aimed at comparing different methods to estimate the [Formula: see text] from an IPD meta-analysis. METHODS: We compared four methods: the area between Kaplan-Meier curves (experimental vs. control arm) ignoring the trial effect (Naïve Kaplan-Meier); the area between Peto curves computed at quintiles of event times (Peto-quintile); the weighted average of the areas between either trial-specific Kaplan-Meier curves (Pooled Kaplan-Meier) or trial-specific exponential curves (Pooled Exponential). In a simulation study, we varied the between-trial heterogeneity for the baseline hazard and for the treatment effect (possibly correlated), the overall treatment effect, the time horizon [Formula: see text], the number of trials and of patients, the use of fixed or DerSimonian-Laird random effects model, and the proportionality of hazards. We compared the methods in terms of bias, empirical and average standard errors. We used IPD from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) and its updated version MAC-NPC2 for illustration that included respectively 1,975 and 5,028 patients in 11 and 23 comparisons. RESULTS: The Naïve Kaplan-Meier method was unbiased, whereas the Pooled Exponential and, to a much lesser extent, the Pooled Kaplan-Meier methods showed a bias with non-proportional hazards. The Peto-quintile method underestimated the [Formula: see text], except with non-proportional hazards at [Formula: see text]= 5 years. In the presence of treatment effect heterogeneity, all methods except the Pooled Kaplan-Meier and the Pooled Exponential with DerSimonian-Laird random effects underestimated the standard error of the [Formula: see text]. Overall, the Pooled Kaplan-Meier method with DerSimonian-Laird random effects formed the best compromise in terms of bias and variance. The [Formula: see text] estimated with the Pooled Kaplan-Meier method was 0.49 years (95% CI: [-0.06;1.03], p = 0.08) when comparing radiotherapy plus chemotherapy vs. radiotherapy alone in the MAC-NPC and 0.59 years (95% CI: [0.34;0.84], p < 0.0001) in the MAC-NPC2. CONCLUSIONS: We recommend the Pooled Kaplan-Meier method with DerSimonian-Laird random effects to estimate the difference in restricted mean survival time from an individual-patient data meta-analysis.

[uPA/PAI-1, Oncotype DX™, MammaPrint(®). Prognosis and predictive values for clinical utility in breast cancer management]. / uPA/PAI-1, Oncotype DX™, Mammaprint(®). Valeurs pronostique et prédictive pour une utilité clinique dans la prise en charge du cancer du sein.

CONTEXT AND AIMS: Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions. METHODS: The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence. CONCLUSIONS: Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking.

[Cost of high-throughput sequencing (NGS) technologies: Literature review and insights]. / Coût des technologies de séquençage haut débit (NGS) : revue de la littérature et enseignements.

Although high-throughput sequencing technologies (Next-Generation Sequencing [NGS]) are revolutionizing medicine, the estimation of their production cost for pricing/tariffication by health systems raises methodological questions. The objective of this review of cost studies of high-throughput sequencing techniques is to draw lessons for producing robust cost estimates of these techniques. We analyzed, using an eleven item analysis framework, micro-costing studies of high-throughput sequencing technologies (n=17), including two studies conducted in the French context. The factors of variability between the studies that we identified were temporality (early evaluation of the innovation vs. evaluation of a mature technology), the choice of cost evaluation method (scope, micro- vs. gross-costing technique), the choice of production steps observed and the transposability of these studies. The lessons we have learned are that it is necessary to have a comprehensive vision of the sequencing production process by integrating all the steps from the collection of the biological sample to the delivery of the result to the clinician. It is also important to distinguish between what refers to the local context and what refers to the general context, by favouring the use of mixed methods to calculate costs. Finally, sensitivity analyses and periodic re-estimation of the costs of the techniques must be carried out in order to be able to revise the tariffs according to changes linked to the diffusion of the technology and to competition between reagent suppliers.

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma.

OBJECTIVES: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin's lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting. METHODS: We used a decision-analytic semi-Markov model with four health states and 1-month cycles. Resource use was prospectively collected in the Inter-B-NHL ritux 2010 trial (NCT01516580). Transition probabilities were assessed from patient-level data from the trial (n = 328). In the base case analysis, direct medical costs from the French National Insurance Scheme and life-years (LYs) were computed in both arms over a 3-year time horizon. Incremental net monetary benefit and cost-effectiveness acceptability curve were computed through a probabilistic sensitivity analysis. Deterministic sensitivity analysis and several sensitivity analyses on key assumptions were also conducted, including one exploratory analysis with quality-adjusted life years as the health outcome. RESULTS: OS and EFS benefits shown in the Inter-B-NHL ritux 2010 trial translated into the model by rituximab-chemotherapy being the most effective and also the least expensive strategy over the chemotherapy strategy. The mean difference in LYs between arms was 0.13 [95% CI 0.02; 0.25], and the mean cost difference € - 3 710 [95% CI € - 17,877; € 10,525] in favor of rituximab-chemotherapy group. For a € 50,000 per LY willingness-to-pay threshold, the probability of the rituximab-chemotherapy strategy being cost-effective was 91.1%. All sensitivity analyses confirmed these findings. CONCLUSION: Adding rituximab to LMB chemotherapy in children and adolescents with high-risk mature B-cell non-Hodgkin's lymphoma is highly cost-effective in France. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01516580.

A Case-Only Genome-Wide Interaction Study of Smoking and Bladder Cancer Risk: Results from the COBLAnCE Cohort.

Bladder cancer (BC) is the 6th most common cancer worldwide, with tobacco smoking considered as its main risk factor. Accumulating evidence has found associations between genetic variants and the risk of BC. Candidate gene-environment interaction studies have suggested interactions between cigarette smoking and NAT2/GSTM1 gene variants. Our objective was to perform a genome-wide association case-only study using the French national prospective COBLAnCE cohort (COhort to study BLAdder CancEr), focusing on smoking behavior. The COBLAnCE cohort comprises 1800 BC patients enrolled between 2012 and 2018. Peripheral blood samples collected at enrolment were genotyped using the Illumina Global Screening Array with a Multi-Disease drop-in panel. Genotyping data (9,719,614 single nucleotide polymorphisms (SNP)) of 1674, 1283, and 1342 patients were analyzed for smoking status, average tobacco consumption, and age at smoking initiation, respectively. A genome-wide association study (GWAS) was conducted adjusting for gender, age, and genetic principal components. The results suggest new candidate loci (4q22.1, 12p13.1, 16p13.3) interacting with smoking behavior for the risk of BC. Our results need to be validated in other case-control or cohort studies.

Design and testing of an optical instrument for skin flap monitoring.

Flap procedures are complex surgical tools widely used in reconstructive surgery. Flap ischemia is one of the most dangerous complications, both during the surgical procedure and during the patient's recovery, which can quickly lead to tissue necrosis (flap loss) with serious medical and psychological consequences. Today, bedside clinical assessment remains the gold standard for flap monitoring, but timely detection of flap ischemia is a difficult and challenging task, so auxiliary techniques are needed to support flap monitoring. Here we present a prototype of a new optical diagnostic tool, based on visible light absorption in diffuse reflectance spectroscopy, for non-invasive, continuous, real-time monitoring of flaps. The proposed approach is assessed by monitoring flap ischemic scenarios induced on pig animal models. The results obtained support that the proposed approach has great potential, not only for prompt detection of ischemia (in seconds), but also for clear differentiation between an arterial occlusion and venous occlusion.

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

PURPOSE: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting. PARTICIPANTS: COBLAnCE (COhort to study BLAdder CancEr) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up. FINDINGS TO DATE: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy. FUTURE PLANS: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making.

Impact of Competition Versus Centralisation of Hospital Care on Process Quality: A Multilevel Analysis of Breast Cancer Surgery in France.

BACKGROUND: The implications of competition among hospitals on care quality have been the subject of considerable debate. On one hand, economic theory suggests that when prices are regulated, quality will be increased in competitive markets. On the other hand, hospital mergers have been justified by the need to exploit cost advantages, and by evidence that hospital volume and care quality are related. METHODS: Based on patient-level data from two years (2005 and 2012) we track changes in market competition and treatment patterns in breast cancer surgery. We focus on technology adoption as a proxy of process quality and examine the likelihood of offering two innovative surgical procedures: immediate breast reconstruction (IBR), after mastectomy and sentinel lymph node biopsy (SLNB). We use an index of competition based on a multinomial logit model of hospital choice which is not subject to endogeneity bias, and estimate its impact on the propensity to receive IBR and SLNB by means of multilevel models taking into account both observable patient and hospital characteristics. RESULTS: The likelihood of receiving these procedures is significantly higher in hospitals located in more competitive markets. Yet, hospital volume remains a significant indicator of quality, therefore benefits of competition appear to be sensitive to the estimates of the impact of volume on care process. In France, the centralisation policy, with minimum activity thresholds, have contributed to improving breast cancer treatment between 2005 and 2012. CONCLUSION: Finding the right balance between costs and benefits of market competition versus concentration of hospital care supply is complex. We find that close to monopolistic markets do not encourage innovation and quality in cancer treatment, but highly competitive markets where many hospitals have very low activity volumes are also problematic because hospital quality is positively linked to patient volume.

Sentinel lymph node biopsy versus selective neck dissection in patients with early oral squamous cell carcinoma: A cost analysis.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) has been proved to be as efficient as selective neck dissection (SND) for the treatment of occult metastases in T1-T2cN0 oral squamous cell carcinoma (OSCC). The aim of our study was to assess and compare the cost of these two surgical procedures. PATIENTS AND METHODS: This retrospective cost analysis includes consecutive patients treated between 2012 and 2017 in two French hospitals either by SLNB or SND. Hospital cost (hospital stay for initial surgery and re-hospitalizations over a period of 60 days after the initial surgery), the length of hospital stay for the initial surgery and the perioperative management were described and compared between the two techniques. The propensity score regression adjustment method was used to address selection bias. RESULTS: Ninety-four patients underwent SLNB procedure and seventy-seven patients underwent SND. The length of hospital stay for initial surgery was lower in SLNB group: 5.8 days (SD: 3.8) versus 9.2 days (SD: 5) in the SND group. Hospital costs were lower in SLNB group: €7 489 (standard deviation: €3 691) versus €8 886 (standard deviation: €4 381) but this difference was not significant after propensity score regression adjustment. The rate of complication, the delay of full oral feeding and postoperative drainage were lower in SLNB group. CONCLUSION: SLNB in T1-T2cN0 OSCC is less invasive than SND with fewer complications, a shorter length of hospital stay and favorable perioperative management. This study shows that this technique could be also less expensive than SND.

A phase III randomized trial of weight loss to reduce cancer-related fatigue among overweight and obese breast cancer patients: MEDEA Study design.

BACKGROUND: Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology. METHODS: Patients (N = 220) with stage I-III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500-1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225-300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40. DISCUSSION: MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304924.

The impact of research on hospital costs of care: an empirical study.

The goal of this study was to examine the impact of research activities on hospital costs and lengths of stay in French public hospitals. Our data consist of a random sample of 30000 inpatient stays in 38 hospitals that were extracted from the French Hospital Cost Survey database. Hospital characteristics were added using data from a French national survey and performing a bibliometric study. This is a retrospective study of hospitalizations. We used multilevel modelling. We considered separate models to explain the cost per day and the length of hospital stay (LOS). Research output was defined based on the quartiles of the distribution of the number of impact-weighted scientific publications produced in our sample of hospitals over a 6-year period. Research production was associated with a higher cost of care. The cost per day was 19% higher in hospitals in the 3rd quartile and 42% higher in hospitals in the 4th quartile compared to that in hospitals that were not involved in research activities. This result was sensitive to the type of care under consideration. The effect was stronger in oncology but not significant in routine care. Scientific production did not impact the LOS.

Impact of COVID-19 on healthcare organisation and cancer outcomes.

BACKGROUND: Changes in the management of patients with cancer and delays in treatment delivery during the COVID-19 pandemic may impact the use of hospital resources and cancer mortality. PATIENTS AND METHODS: Patient flows, patient pathways and use of hospital resources during the pandemic were simulated using a discrete event simulation model and patient-level data from a large French comprehensive cancer centre's discharge database, considering two scenarios of delays: massive return of patients from November 2020 (early-return) or March 2021 (late-return). Expected additional cancer deaths at 5 years and mortality rate were estimated using individual hazard ratios based on literature. RESULTS: The number of patients requiring hospital care during the simulation period was 13,000. In both scenarios, 6-8% of patients were estimated to present a delay of >2 months. The overall additional cancer deaths at 5 years were estimated at 88 in early-return and 145 in late-return scenario, with increased additional deaths estimated for sarcomas, gynaecological, liver, head and neck, breast cancer and acute leukaemia. This represents a relative additional cancer mortality rate at 5 years of 4.4 and 6.8% for patients expected in year 2020, 0.5 and 1.3% in 2021 and 0.5 and 0.5% in 2022 for each scenario, respectively. CONCLUSIONS: Pandemic-related diagnostic and treatment delays in patients with cancer are expected to impact patient survival. In the perspective of recurrent pandemics or alternative events requiring an intensive use of limited hospital resources, patients should be informed not to postpone care, and medical resources for patients with cancer should be sanctuarised.

Cost-effectiveness of preoperative magnetic resonance imaging to optimize surgery in ductal carcinoma in situ of the breast.

PURPOSE: Complete surgical excision is the main factor for successful breast-conserving surgery in patients with ductal carcinoma in situ (DCIS) of the breast. Preoperative magnetic resonance imaging (MRI) may allow surgery optimization in this indication. From an economic standpoint, systematic preoperative MRI is associated with an extra cost, which may be offset by a decrease in the number of re-interventions. We performed an economic evaluation alongside IRCIS randomised controlled trial (NCT01112254) to determine whether systematic preoperative MRI in DCIS is a cost-effective strategy. METHODS: 360 patients were included in IRCIS trial. Costs were assessed from the French national health insurance perspective. Resource use was prospectively collected during a 6-month period after randomisation. We estimated the mean cost per averted re-intervention. RESULTS: Despite extra costs due to MRI and additional biopsies, difference in total costs between arms was not statistically significant (mean cost of €9980 in MRI arm and €9682 in no MRI arm, cost difference: €298 [CI95% : -470; 1063]). There was a non-significant decrease in the rate of re-hospitalisations for positive or close margins (20% in MRI arm versus 27% in No MRI arm, difference -7% [CI95% : -17; 3]). At a willingness to pay of €500 to avert a re-intervention, the probability that MRI strategy is cost-effective was 93%. CONCLUSION: Systematic preoperative MRI in patients with DCIS of the breast may be a cost-effective strategy. However, the modest clinical benefit associated with such a strategy limits the interest for this procedure in routine practice given the current MRI techniques.

A microsimulation model to assess the economic impact of immunotherapy in non-small cell lung cancer.

INTRODUCTION: Immunotherapy has become the standard of care in advanced non-small cell lung cancer (NSCLC). We aimed to quantify the economic impact, in France, of anti-PD-1 therapy for NSCLC. METHODS: We used patient-level data from the national ESCAP-2011-CPHG cohort study to estimate time to treatment failure and mean cost per patient for the four label indications approved by the European Medicines Agency (EMA) for NSCLC in May 2018. To compute the budget impact, we used a microsimulation model to estimate the target populations of anti-PD-1 therapy over a 3-year period, which were combined with the annual cost of treatment. RESULTS: Overall, 11 839 patients with NSCLC were estimated to be eligible for anti-PD-1 therapy 3 years after the introduction of anti-PD-1 therapies. The mean annual cost per patient in the control group ranged from €2671 (95% CI €2149-3194) to €6412 (95% CI €5920-6903) across the four indications. The mean annual cost of treatment for the four EMA-approved indications of anti-PD-1 therapy was estimated to be €48.7 million in the control group and at €421.8 million in the immunotherapy group. The overall budget impact in 2019 is expected to amount to €373.1 million. In the sensitivity analysis, flat doses and treatment effect had the greatest influence on the budget impact. CONCLUSION: Anti-PD-1 agents for NSCLC treatment are associated with a substantial economic burden.