Search

Introduction: Immune checkpoint inhibitors (ICIs) are a key component of standard anticancer systemic therapy. While their immune-related adverse effects (irAEs) have been widely described, there are few data on grade≥3 irAEs. The primary aim of our descriptive study was to evaluate their incidence and characteristics., Methods: An observational, retrospective, monocentric study was conducted. It included patients with locally advanced or metastatic melanoma, non-small cell lung cancer or renal cell carcinoma who initiated ICI therapy between 2016-2021 and experienced at least one grade≥3 irAEs coded according to the MedDRA® system., Results: All cancer types and ICIs combined, the incidence of grade≥3 irAEs was estimated at 11.7% [9.6-13.9]. These were mainly hepatobiliary (22%), gastrointestinal (17%), musculoskeletal (16%) and respiratory (16%) disorders. They occurred on average 6.2±6.2 months after the start of treatment, resulting in hospitalization or prolonged hospitalization in over 40 and 20% of cases, respectively. Resolution without sequelae was observed in 56% of cases, but four patients died., Discussion: This real-world study investigated three cancers and several ICIs, unlike previously published studies that focused on a single cancer and/or one ICI. It provides a better understanding of grade≥3 irAEs, most of which are reversible, which an aim to optimize patient care., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Aims: Hospitalizations for adverse drug reactions (ADR-HA) have increased over the last decade, but the impact of ADR-HA has rarely been evaluated. The aim of this study was to estimate the economic burden of ADR-HA in France., Methods: A partial economic evaluation from the viewpoint of French public health insurance was performed, based on a previous pharmacovigilance study (IATROSTAT) performed in 2018 in public hospital medical units. The cost included direct medical costs, collected retrospectively, from the French hospital discharge database. The economic burden was estimated by calculating the total cost per ADR-HA patient (cost of hospital stays, additional daily cost of specific stays, such as in a resuscitation, intensive care or continuous surveillance unit, drug products and medical devices in addition to Healthcare Resource Group-based tariffs, and specific outpatient consultations and other clinical and technical medical procedures, over 3 months as from the first day of ADR-HA). The robustness of the results was assessed using a one-way deterministic sensitivity analysis of cost factors applying tariffs from 2023 instead of 2018., Results: According to the 2018 tariffs (vs. 2023), the mean total cost per patient with ADR-HA was estimated at €5208 ± €3719 (vs. €5974 ± €4232) ranging from €514 to €23 355 (vs. €618 to €27 380). The total cost for 196 patients with ADR-HA admitted to a sample of French public hospitals was estimated at €1 020 549 (vs. €1 170 960). It could be estimated at €1.3 billion at the national level., Conclusions: In addition to the increase in the number of expensive drugs, the ageing population and polypharmacy, the economic impact of serious ADR-HA weighs heavily on healthcare spending., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: To ensure the safe use of oral anticancer drugs, oncology pharmacy consultations (OPCs) have been established in France. They are conditioned by the needs, expectations, and involvement of the patients in their care. Thus, it is essential to elicit their preferences. The discrete-choice experiment (DCE) is a method recommended by the ISPOR for such a task. The "selection and validation of attributes and their values" step is fundamental in this process. In this context, the aim of this study was to present our research approach to identify and validate the attributes that characterize an OPC and their values., Methods: Due to the lack of relevant published data in the literature, the focus-group method was used in accordance with good research practices for the application of conjoint-analysis of the ISPOR. The two-round Delphi method was used to validate the attributes and their values identified by the focus-group method., Results: The focus-group method enabled identification of nine attributes. Thirty-seven healthcare professionals at a national level, including 30 pharmacists and seven physicians, were selected to take part in the Delphi procedure. Seven attributes (frequency, planification, operation mode, duration, content, written support, and report) and their values were thus validated., Conclusion: Based on these results, the next step will be to elicit patient preferences for OPCs and to then shed light on the issues of pharmaceutical support for patients by comparing their preferences with those of informal caregivers and, in particular, those of the healthcare professionals involved in their care., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: In a French context of low vaccination coverage for human papillomavirus (HPV) disease, we conducted a study on pharmacy students and community pharmacists to assess their self-reported knowledge about HPV infection and vaccination and their perceptions of vaccination., Material and Methods: A prospective volunteered-based study was conducted in the French Franche-Comté region based on a questionnaire targeting pharmacy students (from the 2nd to 6th years) and community pharmacists., Results: All in all, 220 students and 55 pharmacists completed a questionnaire. Fewer than a third knew which HPV genotypes are considered to be high-risk (p-value = 0.11) and were aware of the diversified nature of HPV-induced cancers (p-value = 0.02). Their overall level of general knowledge about vaccination was estimated to be good by 62% of students and 85% of pharmacists (p-value = 10 -3 ). More than 75% of students and pharmacists considered that HPV vaccination has a positive benefit-risk balance (p-value = 0.44) but that its low coverage is due to non-confirmed adverse events that were suggested in the past (p-value = 0.60). Pharmacists had a better perception of the safety of HPV vaccination (84% versus 64%, p-value = 6·10 -3 ). More than 50% of students and pharmacists agreed with mandatory HPV vaccination for girls and boys (11-14 years)., Conclusion: This study allowed us to assess the knowledge of students and community pharmacists and their more or less favorable perceptions of HPV vaccination. It helped us to suggest their needs in terms of practical training. Future changes should include pharmacists in the implementation of public health policies and to improve vaccination coverage., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: French healthcare students are required to carry out primary prevention interventions as part of the Healthcare Service by Healthcare Students (HSHS). The purpose of this study was to explore students' perceptions of preparedness to address the public's concerns about antibiotic use and how their perceptions changed after implementing their intervention., Methods: A questionnaire was sent twice during the 2020-2021 academic year to 920 multidisciplinary healthcare students (nursing, medicine, physiotherapy, pharmacy and midwifery students) enrolled in the HSHS in Franche-Comté (HSHS-FC)., Results: This study included 870/920 students (94.6%). Medical and pharmacy students were the most concerned about the issue of antimicrobial resistance. Before enrollment in the HSHS-FC, 463 of the 870 students included (53.2%) reported having sufficient knowledge about antibiotics to lead preventive interventions, reaching 87.9% (58/66) for pharmacy students. Despite this relative lack of knowledge, 77.2% of students felt confident to promote the appropriate use of antibiotics in the healthcare service context. This rate ranged from 68.0% (17/25) for midwifery students to 93.9% (62/66) for pharmacy students. Irrespective of the topic of the intervention, students significantly improved their knowledge and ability to promote antibiotic use after training in the HSHS-FC., Conclusions: Theoretical prerequisites and a feeling of concern vary widely depending on the curriculum. The HSHS-FC promotes multidisciplinary collaboration and can contribute to improving students' knowledge. The support of an expert in antimicrobial resistance may be necessary to validate the content of the interventions proposed by the students., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: To assess health-related quality of life (QoL) in caregivers of elderly patients with chronic disabilities receiving, or not receiving, social worker support. Methods: This multicenter open-label randomized study assigned caregivers to receive an information booklet, exclusively, or with social worker support. Caregivers completed Short Form-36 (SF-36) and Hospital Anxiety Depression Scale quarterly, and Zarit Burden Interview each semester, for 24 months. We reported caregiver QoL mean changes at 12 and 24 months (M12, M24). Longitudinal QoL analysis up to M24 used mixed models for repeated measures (MMRM). Results: Among the 179 caregivers randomized from 2015 to 2019, the SF-36 physical and mental component summary showed no significant changes at M12 and M24, in terms of neither anxiety nor burden. However, depression significantly increased (M12: 1.4 ± 4.0; M24: 1.7 ± 4.1) with significant adjusted mean increase using MMRM at M24: 3.4 [0.6-2.5] in the control group, exclusively. Conclusion: These findings call for better recognition of the social support to prevent caregiver QoL deterioration and alleviate their depression early in the course of the disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02626377., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Pozet, Darnis, Bonnet, Meurisse, Dabakuyo-Yonli, Lejeune, Fagnoni, Gaimard, Manckoundia, Quibel, Marchand, Anota and Nerich.)

Introduction: Chemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX ® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX ® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence., Methods: Clinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX ® test or SoC) and a Markov model to capture long-term outcomes., Results: In the base case, the Oncotype DX ® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX ® testing was the dominant strategy., Discussion: Widespread implementation of Oncotype DX ® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system., Competing Interests: EC, MB, VN, DH, J-SF and RR were paid an honorarium from Creativ-Ceutical for their expertise during this project. ICO received funding from Creativ-Ceutical for the expertise of MB and J-SF on this project. EC also received grants for a translational research project from Novartis SAS and honoraria from Novartis SAS, Exact Sciences, Astra Zeneca, MSD, Cancerodigest, Pfizer, Daiichi Sankyo, and Pierre Fabre outside of this work. J-SF also received consulting fees from Pfizer, Lilly, Novartis, Astra Zeneca, Clovis Oncology, GSK, Gilead, Daiichi Sankyo, Seagen, Exact Sciences, and MSD outside of this work, as well as honoraria from Lilly, Novartis, Astra Zeneca, Gilead, Daiichi Sankyo, Seagen, and MSD outside of this work. DH and RR reported honoraria from Veracyte outside of this work. DH also received grants from Gilead outside of this work. OC was employed by Creativ-Ceutical. Creativ-Ceutical was contracted by Exact Sciences to conduct this study., (Copyright © 2023 Curtit, Bellanger, Nerich, Hequet, Frenel, Cristeau and Rouzier.)

Breast cancer (BC) is a major health concern in Lebanon, with an increasing incidence rate due to advancements in treatment modalities. Evaluating the impact of the BC and its treatment on a woman's Health-Related Quality of Life (HRQoL), and comparing these patterns before and after breast conserving surgery is important to identify areas where interventions may be needed to improve the overall well-being of women with BC. This study aimed to evaluate the HRQoL pre and post-operative breast conserving surgery and just prior to initiation of adjuvant therapy in newly diagnosed patients with BC in Lebanon, specifically focusing on changes in body image. A prospective cohort study was conducted on 120 patients in two health care facilities in Lebanon, collecting sociodemographic and clinical data, and using the EORTC QLQ-C30 and QLQ-BR23 questionnaires to evaluate HRQoL. The outcomes were measured at baseline and then one-day post-operative breast surgery. Results revealed a statistically and clinically significant decrease in body image (mean difference of 8.1 points (95% 4.3;11.1)), physical functioning (mean difference of 6.1 points (95% 3.3;8.5)), and emotional functioning (mean difference of -8.4 points (95%-12.4; -4.9) after surgery. Positive change of physical functioning score was observed among married women. Positive change of emotional functioning score was observed among patients with poor body image score and high future perspective score. Our findings provide valuable insights for clinicians and researchers on the impact of breast conserving surgery on HRQoL in Lebanese women., (© 2023. The Author(s).)

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources., (Copyright © 2022. Published by Elsevier Inc.)

Background: The potential effects of breast cancer (BC) on health-related quality of life (HRQoL) should be considered in clinical and policy decision-making, as the economic burden of BC management is currently assessed. In the last decades, time-to-HRQoL score deterioration (TTD) has been proposed as an approach to the analysis of longitudinal HRQoL in oncology. The main objectives of the current study were to investigate the evolution of the utility values in BC patients after diagnosis and during follow-ups and to evaluate the TTD in utility values among women in all stages of BC., Methods: Health-state utility values (HSUV) were assessed using the EuroQol 5-Dimension 3-Level at diagnosis, at the end of the first hospitalization and 3 and 6 months after the first hospitalization. For a given baseline score, HSUV was considered to have deteriorated if this score decreased by ≥ 0.08 points of the EQ-5D utility index score and ≥ 7 points of the EQ visual analogue scale. TTD curves were calculated using the Kaplan-Meier estimation method., Results: Overall 381 patients were enrolled between February 2006 and February 2008. The highest proportions of respondents at the baseline and all follow-ups reporting some and extreme problems were in pain discomfort and anxiety/depression dimensions; more than 80% of patients experienced a deterioration in EQ-5D utility index score and EQ VAS score with a median TTD of 3.15 months and 6.24 Months, respectively., Conclusions: BC patients undergoing therapy need psychological support to cope with their discomfort, pain, depression, anxiety, and fear during the process of diagnosis and treatment to improve their QoL., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aim of the Study: Serious adverse drug reactions account for 3.6% of French hospital admissions. Of these, 48.5% are, at least potentially, preventable. The first aim of post-marketing pharmacovigilance is to detect adverse drug reactions as a safety signal to improve patients' safety. Thus, this study describes the epidemiology of "serious" adverse drug reactions reported between 2015 and 2018 to a regional pharmacovigilance centre and assesses their economic burden., Methods: All "serious" adverse drug reactions reported to a regional pharmacovigilance centre during the four-year study period were collected and cost associated. Only congenital anomalies related to "serious" adverse drug reactions were excluded., Results: All 2585 "serious" adverse drug reactions reported are related to 1242 "serious" individual case safety reports. Among 58.1% of them, patients required hospital admission or a visit to the emergency room with a median cost estimated to €3725 per "serious" individual case safety report. The most "serious" adverse drug reactions reported involved gastrointestinal disorders. Fifteen percent of the imputed drugs had a narrow therapeutic index and the most frequently drug was fluindione. Finally, high relationships with an economic burden were observed for ages over or equal to 65, and imputed drugs from "Blood and Blood-Forming Organs" and "Anti-infectives for systemic use" therapeutic groups., Conclusion: This study provides news data on epidemiology and cost of "serious" adverse drug reactions completing the existing literature. On a regional scale, pharmacovigilance real world data could be interesting for pharmacist clinicians in common practice to improve the good use of drugs., (Copyright © 2021 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: In 2018, the implementation of shared medication reports in pharmacy encourages pharmacists to cooperate with other healthcare professionals. This job allows a decrease of medication errors in elderly. This requires a reorganization of the training offered by universities (initial and continuing training). The aim is to present the results of this pedagogical experimentation., Methods: The experimentation (years 2017-2018 and 2018-2019) required the creation of a course to allow students to carry out a pharmaceutical analysis suitable to elderly people, to set up and carry out a shared medication report in pharmacy. Then, during their 6th year internship, students had to carry out at least one shared medication report per month. A monthly follow-up was organized with a database online., Results: Sixty-four students and 35 internship supervisors participated in the experimentation. All the students improved their ease in using clinical pharmacy tools (pharmaceutical analysis, pharmaceutical interventions, assessment of adherence, etc.). They carried out 345 shared medication reports. In 24.3% of cases, an improvement in the prescription was proposed to the doctor (general practitioner or specialist). For 80% of the internship supervisors, the initial training of the students helped to set up this new pharmacy activity., Conclusions: This teaching is appreciated by students and internship supervisors. It enabled the adoption of the various tools essential for carrying out shared medication reports in pharmacy. Shared medication reports reinforce the multidisciplinary work of pharmacists, especially with general practitioners., (Copyright © 2021 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: No study has focused on the economic burden in non-Hodgkin lymphoma (NHL) survivors, even though this knowledge is essential. This study reports on health care resource use and associated health care costs as well as related factors in a series of 1671 French long-term NHL survivors., Methods: Health care costs were measured from the payer perspective. Only direct medical costs (medical consultations, outpatient treatments, hospitalizations, and medical transport) in the past 12 months were included (reference year 2015). Multiple linear regression was used to search for explanatory factors of health care costs., Results: In total, 1100 survivors (66%) reported having used at least 1 health care resource, and 867 (52%) reported having used at least 1 outpatient treatment. After the authors accounted for missing data, the mean health care cost was estimated at €702 ± €2221. Hospitalizations and outpatient treatments were the main cost drivers. Sensitivity analyses confirmed the robustness of the results. For the 1100 survivors who reported using at least 1 health care resource, the mean health care cost was €1067 ± €2268. Several factors demonstrated statistically significant relationships with health care costs. For instance, cardiovascular disorders increased costs by 66% ± 16%. In contrast, rituximab or autologous stem cell transplantation as initial therapy had no effect on health care costs., Conclusions: The consideration of economic constraints in health care is now a reality. This retrospective study reports on a better understanding of health care resource use and associated health care costs as well as related factors. It may help health care professionals in their ongoing efforts to design person-centered health care pathways., (© 2021 American Cancer Society.)

Introduction: Soft tissue sarcomas (STSs) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available after the conventional first-line regimen. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS. This led to a FDA approval in 2015, but real-world evidence is still required, complementary to the pivotal phase II and III trials., Methods: One hundred twenty-six patients with STS, treated by trabectedin between 2002 and 2019, were analyzed in this retrospective study, in two French centers. The effects of trabectedin on survival, response, and toxicity were described. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin., Results: Three median cycles were administered per patient (1-79). Among the 113 patients analyzed for efficacy, the median progression-free survival was 3.0 months (95% CI: 2.3-4.8), with an overall survival of 12.3 months (95% CI: 10.2-16.9). The rate of disease control was 46% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression-free survival and overall survival of 13.3 months (95% CI: 2.3-18.7) and 27.8 months (95% CI: 3.2-64.7), respectively. Adverse events were manageable., Discussion and Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma. Combinatory regimens are under clinical trials to optimize the place of this chemotherapy., (© 2022 S. Karger AG, Basel.)

Background: In the past few decades, Lebanon has witnessed a significant increase in the incidence rates of women diagnosed with breast cancer. This increase, which is associated with the advancements in treatment modalities, emphasizes the need to evaluate the health-related quality of life (HRQoL) of women with breast cancer and to compare its patterns before and after breast-conserving surgery (BCS)., Objective: This study aims to describe changes in HRQoL according to body image pre- and post-BCS and just before initiation of adjuvant therapy in newly diagnosed patients with breast cancer in Lebanon., Methods: A prospective cohort study targeting Lebanese women newly diagnosed with breast cancer and who have an indication for BCS will be conducted in 2 health care facilities. Baseline characteristics and clinical data will be collected. The European Organization for Research and Treatment of Cancer Quality-of-Life cancer-specific and breast cancer-specific questionnaires will be used to assess HRQoL. The outcomes will be measured at baseline and 1 day after breast surgery. The primary outcome will be the body image dimensions of the Quality-of-Life breast cancer-specific questionnaire. Statistical analyses will include descriptive statistics, paired 2-tailed t test, and stepwise multiple regression. A total of 120 patients will be required., Results: A total of 120 patients were enrolled in the study. Future outcomes will be published in professional peer-reviewed health-related research journals., Conclusions: This study is strengthened by its follow-up nature, allowing us to draw conclusions about causality. The results of this study will identify the most affected components of HRQoL, as well as the factors that could play a role in improving HRQoL among women undergoing BCS. The findings of this study will help decision makers, physicians, and social workers to design a comprehensive program with multidisciplinary components for the management and care of patients with breast cancer in Lebanon., International Registered Report Identifier (irrid): DERR1-10.2196/27893., (©Rana El Haidari, Amelie Anota, Linda Abou-Abbas, Virginie Nerich. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.11.2021.)

Background: The optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness, remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line treatment in mHSPC to the death of the patients., Methods: Two Markov decision-analysis models were developed, one for cohort A "asymptomatic/mildly symptomatic patients in mCRPC", and one for cohort B "symptomatic patients in mCRPC". Each strategy reflects daily practice for mHSPC until progression in mCRPC from the start of first treatment regimen with either docetaxel or abiraterone acetate plus prednisone (AA) in mHSPC to the death of the patient. The cost-effectiveness analysis was performed from the French public health care system perspective. Only direct medical costs were included. Survival data were extracted from results of published randomized clinical trials., Results: For cohort A, docetaxel followed by AA is the most cost-effective therapeutic strategy (€96,925 for 4.24 life-years). For cohort B, docetaxel followed by docetaxel is the most cost-effective therapeutic strategy (€81,463 for 4.05 life-years). Sensitivity analyses confirmed the robustness of our results except for a price reduction of 70% for AA or enzalutamide., Conclusion: Our approach is innovative to the extent that our analysis considers various potential strategies for metastatic prostate cancer (mPC). Our economic evaluation suggests that a price reduction of AA or enzalutamide impacts on the results. This approach must continue, including new drugs for patients with mPC., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Influenza vaccination coverage currently remains below the 75% recommended threshold by the World Health Organization. To correct this situation, experiments have been successively carried out in France to enable community pharmacists to vaccinate at-risk populations. In this context, a study was conducted with pharmacists from the French Franche-Comté region to evaluate their positioning, needs and expectations regarding influenza vaccination at community pharmacies., Materials and Methods: A survey was created and sent to licensed pharmacists in March of 2018. This consisted of 4 parts: characteristics of the community pharmacy; positioning of the pharmacist regarding vaccinations carried out at the pharmacy; training needs and expectations; and willingness to implement vaccinations., Results: The participation rate in this survey was 32% (137/427). More than 90% of the pharmacists agreed that community pharmacies' assets were adequate for the implementation of these vaccinations (accessibility and availability), although 52% considered this complicated. Their main fears were reluctance from patients and conflicts of interest with other health professionals authorized to vaccinate (58%). The needs and expectations regarding pharmacy student training were essential for 94% of them as well as continuous training of practicing pharmacists (96%). The willingness of pharmacists to vaccinate stemmed from the fact that influenza vaccination coverage would increase for at-risk subjects (36%)., Conclusion: This survey allowed us to assess the favorable positioning and the real interest of pharmacists from Franche-Comté regarding the influenza vaccination done at community pharmacies, given the proviso that they were given relevant training and allocated adequate resources., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background and Objective: The EORTC Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D) is a new multi-attribute utility instrument derived from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30), a widely used cancer-specific quality-of-life questionnaire. It covers ten dimensions: physical, role functioning, social, emotional functioning, pain, fatigue, sleep, appetite, nausea and bowel problems. To allow national health preferences to be reflected, country-specific valuations are being performed through collaboration between the Multi-Attribute Utility Cancer (MAUCa) Consortium and the EORTC. The aim of this study was to determine the utility weights for health states in the French version of the QLU-C10D., Methods: Valuations were run in a web-based setting in a general population sample of 1033 adults. Utilities were elicited using a discrete-choice experiment (DCE). Data were analyzed by conditional logistic regression and mixed logits., Results: The sample was representative of the general French population in terms of gender and age. Dimensions with the largest impact on utility weights were, in this order: physical functioning, pain and emotional functioning. The impact on utilities was lower for role functioning, nausea, bowel problems and social functioning. The dimensions of sleep, fatigue and lacking appetite were associated with the smallest utility decrement., Conclusion: The results of the present study provide utility weights for the QLU-C10D and offer interesting prospects, as some cancer-specific dimensions also received sizeable utility weights (nausea and bowel problems). In fact, the EQ-5D and the HUI 3 are recommended in France and commonly used for cancer-related CUA; however, both these instruments are generic. The availability of a new cancer-specific utility instrument, such as the QLU-C10D, could improve the quality and the pertinence of future CUA in oncology.

Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.

Introduction: Since the last cancer plan 2014-2019, the assessment of the impact of the disease on caregivers became essential. The quality of caregiving represents an important part of the patient's quality of life. The main objective was to describe the evolution of caregiver's attachment style during the first three years of the disease support., Methods: Caregivers have been included through the ICE study (Informal Carers of Elderly). They were taking care for one near parent at least 60 years of age with a diagnosis of cancer (breast, prostate, colorectal). Caregivers were interviewed at home within three months of inclusion in the ICE study. This longitudinal research based on recorded semi-structured interviews and used one scale (RSQ) to evaluate the attachment style: secure attachment, detached-type insecure, preoccupied-type insecure or fearful-type insecure., Results: The evolution of attachment styles reflect different relational strategies among the 33 caregivers included. The three first times of the disease are differently lived by the caregivers and are impacted by an insecurity form. The attachment style is different depending on the stage of the disease and the impact of the assistance provided shows that caregivers use more detachment relational strategy in the first year. Then, between 3 and 15 months, the attachment style is evolving towards more preoccupied style., Discussion: Detached-type insecure caregiver tend to minimize their signs of distress in the first time of disease. By contrast, preoccupied-type insecure adults tend to maximize distress signals. It's important to consider the specificity of each step of the process to better support caregivers., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The perceptions of healthcare students of vaccines have been poorly explored and appropriate training strategies to address possible confidence gaps concerning vaccination for these future professionals is still a subject of debate., Methods: A questionnaire to assess the perceptions of vaccination and the feeling of preparedness to address patient concerns was submitted to 874 multidisciplinary healthcare students enrolled in the French program "Service Sanitaire des Etudiants en Santé" (SSES). The evolution of their perceptions during the year and the impact of having performed a primary prevention intervention in the context of the SSES program were assessed., Results: In total, 530 students of nursing (42.5%), medicine (31.5%), physiotherapy (11.3%), pharmacy (10.9%), and midwifery (3.8%) completed the questionnaires. Among them, 7.0% carried out an intervention within the topic "vaccination and hygiene" and 93.0% within another topic ("nutrition and physical activity" or "addiction"). A portion of the students showed traits of vaccine hesitancy, including specific concerns about side effects (61.5%) or the number of vaccines in the vaccination schedule (30.0%). They felt ill prepared to address vaccine-hesitant patients, with poor confidence of their knowledge about vaccines (52.5%), their ability to inform patients about the side effects (42.5%), the benefit/risk of adjuvants (51.7%), and the rules for introducing a new vaccine (51.9%). They showed significant differences in perception depending on their curriculum. Misconceptions and hesitancy concerning vaccines were significantly improved after the students had performed the primary prevention intervention, regardless of the topic., Conclusions: A portion of French healthcare students show traits of vaccine hesitancy, with significant differences depending on the courses attended. Programs of health promotion, such as the French SSES program, which includes a primary prevention intervention conducted by multidisciplinary groups of students, may improve the global confidence of healthcare students concerning vaccination., 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 © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Scientific advances in the last decade have highlighted the use of immunotherapy, especially immune checkpoint inhibitors, to be an effective strategy in cancer therapy. However, these immunotherapeutic agents are expensive, and their use must take into account economic criteria. Thus, the objective of the present study was to systematically identify and review published EE related to the use of ipilimumab, nivolumab or pembrolizumab in melanoma, lung cancer, head and neck cancer or renal cell carcinoma, and to assess their quality., Methods: The systematic literature research was conducted on Medline via PubMed and the Cochrane Central Register of Controlled Trials to identify economic evaluations published before July 2018. The quality of each selected economic evaluation was assessed by two independent reviewers using the Drummond checklist., Results: Our systematic review was based on 32 economic evaluations using different methodological approaches, different perspectives and different time horizons. Three-quarters of the economic evaluations are full (n = 24) with a Drummond score ≥ 7, synonymous of "high quality". Among them, 66% reported a strategy that was cost-effective. The most assessed immunotherapeutic agent was nivolumab. In patients with renal cell carcinoma or head and neck cancer, it was less likely to be cost-effective than in patients with melanoma or lung cancer., Conclusions: Whether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available.

Background: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results., Objectives: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases., Data Sources: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019., Study Eligibility Criteria: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster., Methods: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist., Results: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole., Conclusions: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.

Objectives: The aim of the present systematic review was to identify the factors that potentially influence health-related quality of life (HRQoL) in women with breast cancer (BC) in the Middle East., Methods: A systematic search of the PubMed, Ovid Medline, Cochrane, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Ebscohost databases was conducted to identify all relevant articles published in peer-reviewed journals up to April 2018. The keywords were "Health related quality of life", "Breast Cancer", and "Middle East countries". The Newcastle-Ottawa (NOS) scale was used to evaluate the methodological quality of the included studies. Due to the methodological heterogeneity of the identified studies, no statistical pooling of the individual effect estimates was carried out; instead, the results were summarized descriptively., Results: A total of 5668 articles were screened and 33 studies were retained. The vast majority of these studies were cross-sectional and only two were longitudinal prospective studies. Concerning the methodological quality, only 39% were of high quality. Our comprehensive literature review identified several modifiable and non-modifiable risk factors associated with HRQoL, including sociodemographic, clinical, and treatment-related factors as well as behavioral and psychosocial factors., Conclusion: This study has many implications for clinical practice and may provide a framework for establishing policy interventions to improve HRQoL among women with BC. Healthcare systems in the Middle East are encouraged to develop interventional programs targeting modifiable factors, particularly socio-demographic, behavioral, and psychosocial factors.

Purpose: The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the EORTC QLQ-C30, a widely used cancer-specific quality of life questionnaire. It covers ten dimensions: physical, role, social, emotional functioning, pain, fatigue, sleep, appetite, nausea, and bowel problems. To allow national health attitudes to be reflected, country-specific valuations are being performed by collaboration of the Multi-Attribute Utility Cancer (MAUCa) Consortium and the EORTC. The purpose of this paper is to provide German value sets (utility weights) for the QLU-C10D., Methods: Valuations were run in a web-based setting in two general population samples of approximately 2000 adults in total. As the German version of the QLQ-C30 is presently undergoing a revision of the wording of one response category, valuations for both the current and the new version were performed (Germany 1 and 2). Utilities were elicited using a discrete choice experiment (DCE). Data were analyzed by conditional logistic regression and mixed logits., Results: Completion rates were 88.3% (1002/1135) and 90.4% (1016/1124) for Germany 1 and Germany 2 valuations, respectively. Dimensions with the largest impact on utility weights were, in this order: physical functioning, pain, role functioning, social functioning and nausea (same ordering for both German versions). Several violations of the logical ordering of levels were observed for Germany 1; this was largely improved for Germany 2., Conclusion: This study established German utility weights for the cancer-specific utility instrument QLU-C10D.

Introduction: Since the cancer plan, evaluation of professional practices is essential to ensure the implementation of high-quality health care. Assess patient satisfaction is one of the pillars of high-quality health care. The main objective of the study was to assess the satisfaction of patients with early breast cancer taking a hormonal therapy, the secondary objective was to identify factors associated with their satisfaction., Methods: The modified EORTC OUT-PATSAT-35 questionnaire was sent to a sample of patients in Franche-Comté in order to evaluate nine dimensions of satisfaction among which interpersonal skills, provided information, and overall satisfaction. For each dimension, a satisfaction score between 0 (no satisfaction) and 100 (highest satisfaction) was measured. Logistic regression analyses were used to study the factors associated with satisfaction., Results: The mean overall satisfaction score for the 280 patients who answered was 73 [0-100]. Practicing an extra-professional activity was associated with higher satisfaction for several dimensions (odds ratio between 2.80 and 4.12, P<0.05) whereas it was decreased in the case of a modified appetite (odds ratio between 0.27 and 0.52, P<0.05). No link has been shown between satisfaction and adherence., Discussion: The patients were satisfied and several factors impacting their satisfaction were identified, based on a questionnaire that must evolve to take into account the ambulatory aspect of their care. During the consultations, particular attention will be paid to these factors., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Long-term survivors of non-Hodgkin lymphoma (NHL) must cope with treatment complications and late toxicities that affect their health-related quality of life. Little is known about the risk-to-benefit ratio of new agents like rituximab. The impact of treatment regimens and health disorders on long-term fatigue levels was investigated in a cross-sectional study., Methods: Two self-administered questionnaires, the 20-item Multidimensional Fatigue Inventory (MFI-20) and a Life Situation Questionnaire, were mailed in 2015 to NHL survivors enrolled onto 12 successive clinical studies (1993-2010) conducted by the Lymphoma Study Association. Private addresses were obtained for 3317 survivors, of whom 1671 (50%) returned the questionnaires. Severe fatigue was defined as MFI-20 scores ≥60 on dimension scales scored from 0 to 100. Linear regression models were used to assess factors that were linked to increased fatigue levels., Results: The study population included 906 men and 765 women, and the median age was 64 years (age range, 24-95 years). Overall, 811 survivors had received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like chemotherapy, 518 had received high-dose CHOP, and 342 had undergone upfront autologous stem cell transplantation; 829 survivors also had received rituximab. In total, 1100 survivors (66%) reported 1 or more late health disorders. Severe fatigue was reported by 602 survivors (37%). Increased fatigue levels were associated (P < .001) with increased age, obesity, and the presence of health disorders, but not with initial treatment or rituximab., Conclusions: The survey confirms that high proportions long-term NHL survivors have severe fatigue. The results suggest that initial treatment and the receipt of rituximab have no influence on the development of long-term fatigue., (© 2019 American Cancer Society.)

Background: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients., Methods/design: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin., Discussion: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities., Trial Registration: ClinicalTrials.gov, NCT02849899 . Registered on 8 February 2016.

Background: Infections with antibiotic-resistant pathogens in cancer patients are a leading cause of mortality. Cancer patients are treated with compounds that can damage bacterial DNA, potentially triggering the SOS response, which in turn enhances the bacterial mutation rate. Antibiotic resistance readily occurs after mutation of bacterial core genes. Thus, we tested whether cancer chemotherapy drugs enhance the emergence of resistant mutants in commensal bacteria., Methods: Induction of the SOS response was tested after the incubation of Escherichia coli biosensors with 39 chemotherapeutic drugs at therapeutic concentrations. The mutation frequency was assessed after induction with the SOS-inducing chemotherapeutic drugs. We then tested the ability of the three most highly inducing drugs to drive the emergence of resistant mutants of major bacterial pathogens to first-line antibiotics., Results: Ten chemotherapeutic drugs activated the SOS response. Among them, eight accelerated the evolution of the major commensal E. coli, mostly through activation of the SOS response, with dacarbazine, azacitidine and streptozotocin enhancing the mutation rate 21.3-fold (P < 0.001), 101.7-fold (P = 0.01) and 1158.7-fold (P = 0.02), respectively. These three compounds also spurred the emergence of imipenem-resistant Pseudomonas aeruginosa (up to 6.21-fold; P = 0.05), ciprofloxacin-resistant Staphylococcus aureus (up to 57.72-fold; P = 0.016) and cefotaxime-resistant Enterobacteria cloacae (up to 4.57-fold; P = 0.018)., Conclusions: Our results suggest that chemotherapy could accelerate evolution of the microbiota and drive the emergence of antibiotic-resistant mutants from bacterial commensals in patients. This reveals an additional level of complexity of the interactions between cancer, chemotherapy and the gut microbiota., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The immunotherapies known as "inhibitors of checkpoint" (ICP) are monoclonal antibodies used since 2010 and have dramatically modified the management of the advanced or metastatic melanomas. By reactivating the anti-tumoral immune response, these antibodies can activate the immune system in all the tissues with a risk to induce immune related adverse events (IrAE). Thus, the adverse effect's profile of ICP is considered as very different from that usually associated with conventional chemotherapies. The objectives of our retrospective monocentric study were the evaluation of the real life's safety and efficiency of the ipilimumab and the pembrolizumab in patients with an advanced melanoma. Seventy-two patients treated by ipilimumab and\or pembrolizumab between August 1st, 2008 and December 31st, 2016 were investigated. The main IrAE occurring involved the gastro- intestinal, skin, and the endocrine systems. The average onset time of IrAE was 39, 104 and 68 days, respectively and their respective duration was of 67, 50 and 111 days. There were 13 events of grade III and IV along with one death. The overall survival was 5 months for the patients treated in monotherapy with ipilimumab, and 14 months for those treated by pembrolizumab. Our real life's study tends to confirm the current safety profile of ICP treatment. Moreover and according to our analyses, the drug sequence seems to have a global survival impact., (Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Cancer is becoming more prevalent in elderly patient. Due to polypharmacy, older adults with cancer are predisposed to drug-drug interactions. There is also an increasing interest in the use of complementary and alternative medicine (CAM). Thirty to seventy percent of patients with cancer have used CAM. Through pharmaceutical counseling sessions, we can provide advices on herb-drug interactions (HDI). All the patients seen in pharmaceutical counseling sessions were prospectively included. Information was collected during these sessions: prescribed medication (oral anticancer agents (OAA) and other drugs), CAM (phytotherapy especially), and use of over-the-counter (OTC) drugs. If pharmacist considered an interaction or an intervention clinically relevant, the oncologist was notified. Then, a literature review was realized to identify the potential HDI (no interactions, precautions for use, contraindication). Among 201 pharmacist counseling sessions, it resulted in 104 interventions related to 46 HDI, 28 drug-drug interactions and 30 others (wrong dosage, omission…). To determine HDI, we review 73 medicinal plants which are used by our patients with cancer and 31 OAA. A total of 1829 recommendations were formulated about 59 (75%) medical plants and their interaction with an OAA. Herb-drug interactions should not be ignored by healthcare providers in their management of cancer patients in daily practice.

Background: Targeted therapies have transformed the treatment of metastatic clear-cell renal cell carcinoma (mccRCC). Despite the importance of mccRCC, studies on its economic burden in daily practice are sparse. The purpose of this retrospective study was to evaluate cost of illness for 224 patients with mccRCC included in the cohort published by Thiery-Vuillemin et al (Factors influencing overall survival for patients with metastatic clear-cell renal cell-carcinoma in daily practice. Clin Genitourin Cancer 2018; 16:e297-305), and then to determine the explanatory factors of cost of illness., Patients and Methods: The study was performed from the French Public Healthcare System perspective with lifetime horizon. Only direct medical costs were included. Multiple linear regression was used to search for explanatory factors of cost of illness. The robustness of results was assessed., Results: The mean cost of illness was estimated at €71,185 ± 52,683. Outpatient/inpatient treatment and hospitalization represented 76.0% and 19.7% of this cost, respectively. After adjustment, 5 explanatory factors were identified: time of disease control for the metastatic first-line treatment ≥6 months, number of lines of treatment >2, nephrectomy at metastatic stage, lack of metastases at presentation, and age at metastatic diagnosis younger than 65 years. Individually, they increased cost of illness by 128%, 95%, 53%, 53%, and 23%, respectively., Conclusion: Although it is difficult to transpose our economic evaluation results to those obtained in other countries, it should be noted that our findings were consistent with them and robust. To our knowledge, our study was the first to accurately identify explanatory factors of cost of illness. Identifying them could enable us to predict the budgetary effect on a regional level of managing patients who began their first-line treatment with a targeted therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Brain metastases (BM) from adult soft tissue or bone sarcomas are rare, and sparse data exist on their prognostic factors and management., Subjects, Materials and Methods: A retrospective study was conducted in 15 centers of the French Sarcoma Group, plus one Canadian and one Swiss center, to report on clinical, histological, and treatment characteristics and to identify predictive factors of outcome., Results: Between 1992 and 2012, 246 patients with a median age of 50 years (range: 16-86) were managed for BM. BM included 221 cerebral and cerebellar metastases and 40 cases of meningeal sarcomatosis. The most frequent histopathological subtype was leiomyosarcoma (18.7%). Histological grade was high in 118 (48%) cases. Surgery of BM was carried out for 38 (15.5%) patients. Radiotherapy and chemotherapy were administered in 168 (68.3%) and 91 (37.0%) patients, respectively. Irrespective of treatment modality, BM were controlled in 113 patients (45.9%), including 31 partial responses (12.6%) and 18 complete responses (7.3%). The median overall survival from diagnosis of brain metastasis was 2.7 months (range: 0-133). In the multivariate analysis, the following parameters influenced overall survival: chemotherapy (hazard ratio [HR] = 0.38; 95% confidence interval [CI]: 0.26-0.48), surgery (HR = 0.40; 95% CI: 0.22-0.72), stereotactic radiotherapy (HR = 0.41; 95% CI: 0.19-0.90), whole-brain radiotherapy (HR = 0.51; 95% CI: 0.35-0.76), and grade (HR = 0.65; 95% CI: 0.43-0.98)., Conclusion: BM of sarcomas are rare and associated with a dismal outcome. Multidisciplinary management with chemotherapy, radiation therapy, and surgery is associated with a better survival., Implications for Practice: The incidence of brain and meningeal metastasis in bone and soft tissue sarcomas is estimated between 1% and 8%. Published data are derived from small retrospective case series, often in the pediatric population. A prognostic index is important to guide both clinical decision-making and outcomes research, but one such is lacking for adult sarcoma patients with brain metastases. The current study describes brain metastasis in a large cohort of sarcoma patients. This study, conducted within the French Sarcoma Group, describes the natural history of sarcoma brain metastasis and enables the proposal of strategic recommendations for subsequent clinical trials and for the management of such patients., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Background: Recently, a newly developed cancer-specific multiattribute utility instrument based on the widely used health-related quality of life instrument, the European Organisation for Research and Treatment of Cancer QLQ-C30, was introduced: the QLU-C10D. For the elicitation of utility weights, a discrete choice experiment (DCE) was designed. Our aim was to investigate the DCE in terms of individual choice consistency and utility estimate consistency by applying a test-retest design., Methods: We conducted the study in general population samples in Germany and France. The DCE was administered via a web-based self-complete survey using online panels. Respondents were presented 16 choice sets comprising 11 attributes with 4 levels each. Retest was conducted 4 to 6 weeks after first assessment. We used kappa and percentage agreement as measures of choice consistency and both intraclass correlations and mean utility differences as measures of utility estimate consistency., Results: A total of 300 German respondents (31% female, mean age 48 years [SD 14]) and 305 French respondents (46% female, mean age 47 years [SD 16]) completed test and retest assessments. Individual choice consistency was moderate to high (Germany: κ = 0.605, percentage agreement = 80.2%; France: κ = 0.411, percentage agreement = 70.6%). Utility estimate consistency was high when considering intraclass correlations (all >0.79). Mean utility differences were 0.08 in the German sample and 0.05 in the French sample., Conclusions: Results indicate that the designed DCE elicits stable health state preferences rather than guesses or mood-specific or condition-specific judgments. Nevertheless, the identified mean utility differences between test and retest need to be taken into account when determining minimal important differences for the QLU-C10D in future research., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to determine the prevalence of adherence to adjuvant hormonal therapy (AHT) and to identify risk factors for medication non-adherence in clinical practice in patients with early-stage hormone receptor (HR)-positive breast cancer (BC) previously treated with chemotherapy., Methods: We carried out a cross-sectional, observational, prospective, and multicenter survey based on a structured self-report postal questionnaire (35 items investigating six areas). A sample of 474 patients was drawn from 676 patients potentially eligible. The structured and validated Morisky Medication Adherence Scale-4 items was used for measuring medication adherence. An analysis of risk factors for non-adherence to AHT was performed using a two-step approach: univariate, then multivariate analysis., Results: A total of 280 patients out of the 428 analyzed patients participated in the survey, yielding a response rate of 65.4% [60.9-69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1-74.0], corresponding to a high level of adherence. Three risk factors for non-adherence to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003), age less than 65 years (p-value = 0.008), and patient management in a university hospital setting (p-value = 0.014)., Conclusions: Non-adherence is a common, complex, and multidimensional healthcare problem. This better understanding and knowledge of risk factors will allow healthcare providers (such as oncologists, general practitioners, pharmacists) to more easily identify patients at risk for non-adherence and help them provide appropriate information about AHT and its management, thus improving medication adherence in their patients.

Purpose: To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies., Patients and Methods: Two hundred twenty-four consecutive patients with histologically confirmed mccRCC who received targeted therapy on first-line treatment between January 2007 and March 2015 were included. The primary end point was OS for metastatic first-line or second-line treatment. An analysis of prognostic factors of long survival was performed using a 2-step approach: univariate, then multivariate analysis., Results: Median OS [95% confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were identified in first-line treatment: Memorial Sloan Kettering Cancer Center (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval] = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10 -4 ), metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95% confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different prognostic factors predicted long survival: toxicity for first-line treatment discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10 -4 ), duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10 -4 ), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936 [0.607-1.443], respectively, P = .02)., Conclusion: These real-life data confirm the positive impact of targeted therapy in the mccRCC setting. Moreover, it emphasizes the importance of considering many factors in order to better estimate prognosis in patient pretreated with systemic therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The economic evaluation (EE) of healthcare interventions has become a necessity. However, high quality needs to be ensured in order to achieve validated results and help making informed decisions. Thus, the objective of the present study was to systematically identify and review published pancreatic ductal adenocarcinoma-related EEs and to assess their quality., Methods: Systematic literature research was conducted in PubMed and Cochrane to identify published EEs between 2000 and 2015. The quality of each selected EE was assessed by two independent reviewers, using the Drummond's checklist., Results: Our systematic review was based on 32 EEs and showed a wide variety of methodological approaches, including different perspectives, time horizon, and cost effectiveness analyses. Nearly two-thirds of EEs are full EEs (n = 21), and about one-third of EEs had a Drummond score ≥7, synonymous with 'high quality'. Close to 50% of full EEs had a Drummond score ≥7, whereas all of partial EEs had a Drummond score <7 (n = 11)., Conclusions: Over the past 15 years, a lot of interest has been evinced over the EE of pancreatic ductal adenocarcinoma (PDAC) and its direct impact on therapeutic advances in PDAC. To provide a framework for health care decision-making, to facilitate transferability and to lend credibility to health EEs, their quality must be improved. For the last 4 years, a tendency towards a quality improvement of these studies has been observed, probably coupled with a context of rational decision-making in health care, a better and wider spread of recommendations and thus, medical practitioners' full endorsement., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To review the data sources of health-state utility values (HSUVs), as well as their elicitation and use, in 140 breast cancer-related cost-utility analyses (CUAs), and to provide a critical appraisal of these., Methods: A checklist was developed to guide the process of the critical appraisal. It is divided into three parts: the data source (three questions), elicitation method (four questions), and use (ten questions) of HSUVs in CUAs. Two independent reviewers performed the data extraction. A consensus was reached in case of disagreements. Data sources were categorized as "original study," "derived from the literature," or "other.", Results: The data source of HSUVs was always specified. When HSUVs were derived from the literature (90% of cases), the authors referred to a median number of two references as data sources. The critical appraisal of the elicitation of HSUVs in CUAs revealed considerable variability in terms of the quality of the reporting of the data source selection of HSUV. More details were provided by authors when HSUVs were elicited from an original study rather than derived from the literature. The use of HSUVs elicited from an original study was generally better described in terms of the checklist than were those derived from the literature., Conclusions: Based on the developed checklist, we were able to highlight the challenges that authors are facing when trying to adequately report HSUV used in CUAs. Our proposed checklist offers a good starting point for encouraging more explicit and comprehensive reporting of HSUVs in CUAs.

Background: Currently there is little knowledge on real-life sustainability of routine patient-reported outcome (PRO) measurement and the representativeness of collected data., Objectives: The investigation of routine PRO with regard to noncompletion bias and long-term adher- ence, considering the potential impact of mode of assessment (MOA) (paper-pencil vs. electronic PRO [ePRO]) and patient characteristics., Methods: At our department, routine PRO measurement in oncological patients is being done since 2005 using different MOA (paper-pencil assessment until 2011 and ePRO assessment from 2011 onward). We analyzed two different patient groups: patients eligible in both periods (both-MOA group) and patients eligible in only one period (one-MOA group). The primary outcome was PRO noncompletion (100% missing questionnaires). The secondary outcome was poor PRO adherence (>20% missing questionnaires). Multivariate logistic regression models were developed, testing the impact of MOA and patient characteristics on the outcomes in the different patient groups., Results: Data from 1484 eligible patients were included in the analyses. Most of the patients could be included in PRO assessment at least once. PRO noncompletion rates were clearly higher during paper-pencil assessment (odds ratios between 2.72 and 4.31), as were poor PRO adherence rates (odd ratio 2.23). Analyses of potential bias by patient characteristics showed that male patients had a higher risk of poor adherence. Other factors with significant impact were age, country, and cancer diagnosis, but results were indecisive., Conclusions: ePRO increased the feasibility of our clinical routine PRO data for retrospective analyses by increasing completion rates. In general, potential completion bias regarding certain patient characteristics requires attention before generalizing results to the respective populations., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Introduction: Since the introduction of targeted therapies, specific lymphoma mortality has decreased. Possible long-term toxicities, however, are not known yet. This article describes the implementation of the SIMONAL study that investigates the hypothesis of an overconsumption of care after lymphoma treatment with a 10-year follow-up., Methods: After the mandatory regulatory steps (CCTIRS and CNIL) the vital status and address of 5247 patients treated in 131 French centers were retrieved using a secure web portal, in order to send a quality of life after lymphoma questionnaire. After an additional vital status validation request at the center for epidemiologic research and population health (CESP), the questionnaires were sent. Double data entry was performed on the collected data and a request to access data from France's public health insurance scheme information system (SNIIRAM) was formulated., Results: Retrieval of the addresses via the portal has been slow and multiple reminders were needed. The CESP identified 9.4 % additional deaths not known by the treatment centers. Of the 3391 questionnaires sent, the response rate was 50%. A comparison between the responders and non-responders revealed no demographic differences but showed that the responders were more often treated with targeted drugs as they were included in more recent trials., Discussion: Logistic and information technology (IT) aspects rendered the implementation of the SIMONAL study more complex, time consuming and costly. However, using the collected data, many future research questions will be addressed., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown., Objective: The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib 400 /best supportive care [BSC]); S2 (imatinib 400 /imatinib 800 /BSC); S3 (imatinib 400 /sunitinib/BSC); and S4 (imatinib 400 /imatinib 800 /sunitinib/BSC)., Methods: A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed., Results: The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies., Conclusion: Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.

Background: Discrete choice experiments (DCEs) are increasingly used to value aspects of health. An issue with their adoption is that results may be sensitive to the order in which dimensions of health are presented in the valuation task. Findings in the literature regarding order effects are discordant at present., Objectives: To quantify the magnitude of order effect of quality-of-life (QOL) dimensions within the context of a DCE designed to produce country-specific value sets for the EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D), a new utility instrument derived from the widely used cancer-specific QOL questionnaire, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30., Methods: The DCE comprised 960 choice sets, divided into 60 versions of 16 choice sets, with each respondent assigned to a version. Within each version, the order of QLU-C10D QOL dimensions was randomized, followed by life duration in the last position. The DCE was completed online by 2053 individuals in France and Germany. We analyzed the data with a series of conditional logit models, adjusted for repeated choices within respondent. We used F tests to assess order effects, correcting for multiple hypothesis testing., Results: Each F test failed to reject the null hypothesis of no position effect: 1) all QOL order positions considered jointly; 2) last QOL position only; 3) first QOL position only. Furthermore, the order coefficients were small relative to those of the QLU-C10D QOL dimension levels., Conclusions: The order of presentation of QOL dimensions within a DCE designed to provide utility weights for the QLU-C10D had little effect on level coefficients of those QOL dimensions., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Medical progress and the lifestyle modification have prolonged life expectancy, despite the development of chronic diseases. Support and care for older subjects are often provided by a network of informal caregivers composed of family, friends and neighbors, who are essential in helping older persons to continue living at home. It has been shown that the extent and diversity of informal tasks may jeopardize the physical, mental and social wellbeing of caregivers., Methods/design: The aim of the Informal Carers of Elderly cohort is to define, through a longitudinal study, profiles of caregivers of older patients with a diagnosis of one of the following diseases: cancer (breast, prostate, colorectal), neurodegenerative diseases (Parkinson's disease, Alzheimer's disease and similar diseases), neurovascular diseases (stroke), sensory diseases (age-related macular degeneration (AMD)) and heart disease (heart failure). Patients must be at least 60 years old and living in the region of Burgundy-Franche-Comte (France). By following the different phases of the caregiving relationship from the announcement of the diagnosis, it will be possible to assess the quality of life of caregivers, coping strategies, levels of anxiety and depression, social support and the extent of their burden. We will also evaluate the efficacy and efficiency of the implementation of a pragmatic intervention by a social worker to help informal caregivers, through a randomized interventional trial nested in the cohort. Qualitative approaches aimed at studying the caregiver/patient relationship, and situations leading to breakdown of the caregiver relationship will be also undertaken., Discussion: Through an analytical and longitudinal definition of profiles of informal caregivers, this study will gather detailed information on their life courses and their health trajectory by identifying consequences associated with the concept of their role as carers. In addition, the randomized interventional trial will explore the relevance of the implementation of a supportive intervention by a social worker to help caregivers. These data will help to identify strategies that could be used to improve the existing sources of aid and to propose new approaches to help caregivers. This study will provide the opportunity to identify the most relevant means of support adapted to caregivers, and provide an impulse for new health care policies., Trial Registration: ClinicalTrials.gov Identifier: NCT02626377 . Retrospectively registered on 9 December 2015. Protocol date/version: 23 October 2014/version 2.

The economic evaluation (EE) of health care products has become a necessity. Their quality must be high in order to trust the results and make informed decisions. While cost-utility analyses (CUAs) should be preferred to cost-effectiveness analyses in the oncology area, the quality of breast cancer (BC)-related CUA has been given little attention so far. Thus, firstly, a systematic review of published CUA related to drug therapies for BC, gene expression profiling, and HER2 status testing was performed. Secondly, the quality of selected CUA was assessed and the factors associated with a high-quality CUA identified. The systematic literature search was conducted in PubMed, MEDLINE/EMBASE, and Cochrane to identify published CUA between 2000 and 2014. After screening and data extraction, the quality of each selected CUA was assessed by two independent reviewers, using the checklist proposed by Drummond et al. The analysis of factors associated with a high-quality CUA (defined as a Drummond score ≥7) was performed using a two-step approach. Our systematic review was based on 140 CUAs and showed a wide variety of methodological approaches, including differences in the perspective adopted, the time horizon, measurement of cost and effectiveness, and more specially health-state utility values (HSUVs). The median Drummond score was 7 [range 3-10]. Only one in two of the CUA (n = 74) had a Drummond score ≥7, synonymous of "high quality." The statistically significant predictors of a high-quality CUA were article with "gene expression profiling" topic (p = 0.001), consulting or pharmaceutical company as main location of first author (p = 0.004), and articles with both incremental cost-utility ratio and incremental cost-effectiveness ratio as outcomes of EE (p = 0.02). Our systematic review identified only 140 CUAs published over the past 15 years with one in two of high quality. It showed a wide variety of methodological approaches, especially focused on HSUVs. A critical appraisal of utility values is necessary to better understand one of the main difficulties encountered by authors and propose areas for improvement to increase the quality of CUA. Since the last 5 years, there is a tendency toward an improvement in the quality of these studies, probably coupled with economic context, a better and widely spreading of recommendations and thus appropriation by medical practitioners. That being said, there is an urgent need for mandatory use of European and international recommendations to ensure quality of such approaches and to allow easy comparison.

Introduction: Pain management is a major public health problem, especially in oncology. In order to assess professional practice, the IRFC-FC conducted a survey amongst patients with metastatic osteophilic solid tumor in Franche-Comté. The aims were to assess the pain prevalence, and its characteristics, its management and its impact on patients' quality of life in patients in pain., Methods: An observational, prospective and multicenter survey was conducted using a self-report questionnaire. Patients with metastatic breast or prostate cancer managed in 5 day-hospitals of the IRFC-FC over a period of three months were included., Results: Two hundred thirty-three questionnaires were analyzed. Pain prevalence rate was 48.5%. Three quarters of patients in pain had chronic background pain, moderate to severe, with or without breakthrough pain. Considering their pain intensity and their analgesic therapy, 42.0% of patients seem to have an inadequate treatment. Eighty-five percent of treated patients reported to be compliant and felt that their pain was well managed despite a strong impact on their quality of life., Conclusion: The setting of a specific clinical pathway is essential to secure the standardized, optimal and efficient management of patients in pain. The assessment of patient satisfaction and quality of life must be integrated in clinical practice to identify patients in pain for which the treatment is inappropriate., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice., Material and Methods: We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice., Results: From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months)., Conclusions: The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.

Objectives: The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths., Materials and Methods: The cohort of 122 patients was identified from a pharmacy database of patients treated with chemotherapy between 1992 and 2010. The evaluation of benefit obtained by each line was based on TDC duration, defined as the interval between the beginning of the treatment and the date of progressive disease or death., Results: Median TDC durations was 4.15 (0-54.7), 4 (0-21.7), 3.34 (0-29.6), 4.97 (0-29.2), and 3.13 months (0-15) for the fourth to eighth lines, respectively. Time to disease control was longer than 6 months in 34% to 40% of patients treated by lines 4 to 8. The most important factor influencing TDC length beyond the third line was the TDC duration observed in the 2 previous lines of therapy. Median overall survival after the third line was 15.3 months (95% confidence interval, 12-20 months). Factors associated with longer overall survival after 3 lines were performance status lower than 2 (P = 0.0058), no hepatic metastasis (P = 0.0098), no pulmonary metastasis (P = 0.0003), and platinum sensitivity (P = 0.04) CONCLUSIONS: These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months.