Publications by authors named "Frederic Fiteni"

28 Publications

  • Page 1 of 1

Prospective evaluation of sexual health in breast cancer women during the first year of adjuvant hormonal treatment using a cancer patient's dedicated questionnaire: A glaring gap of communication between health professionals and patients.

Breast Cancer Res Treat 2021 Apr 15;186(3):705-713. Epub 2021 Jan 15.

Medical Oncology Department, Institut du Cancer de Montpellier, Montpellier, France.

Purpose: Sexual quality of life (QoL) is affected during and after breast cancer (BC) treatment and is not specifically evaluated with the general health-related quality-of-life questionnaires EORTC QLQ-C30 or QLQ-BR23. A specific questionnaire, the EORTC SHQ-C22, including physical, psychological, and social aspects of sexuality, was recently developed to address this issue in cancer patients.

Methods: A prospective bicentric study was conducted to evaluate the sexual QoL of women with BC during the first year of adjuvant hormonal treatment.

Results: A total of 106 women completed the 3 questionnaires at baseline and 92 of them, at 12 months. At baseline, we showed low sexual satisfaction and importance given to sexual activity and a very low communication with healthcare professionals about this issue. Twelve months later, the importance given to sexuality had increased. While the communication with professionals had improved, it remained at a very low level. We were unable to identify specific clinical factors (chemotherapy, menopausal status, type of surgery or radiotherapy) that would negatively affect the global sexual well-being in BC patients.

Conclusion: The analysis of sexual QoL of BC patients during the first year of hormonal treatment with a recently developed, cancer-dedicated, standardized tool pointed out the need for deeper communication between professionals and patients regarding sexual issues to fill the current gap in care of cancer patients and help patients with adequate intervention and support.
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http://dx.doi.org/10.1007/s10549-020-06062-xDOI Listing
April 2021

Minimally Important Differences for Interpreting EORTC QLQ-C30 Scores in Patients With Advanced Breast Cancer.

JNCI Cancer Spectr 2019 Sep 4;3(3):pkz037. Epub 2019 Jun 4.

European Organisation for Research and Treatment of Cancer, Brussels, Belgium.

Background: We aimed to estimate the minimally important difference (MID) for interpreting group-level change over time, both within a group and between groups, for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) scores in patients with advanced breast cancer.

Methods: Data were derived from two published EORTC trials. Clinical anchors (eg, performance status [PS]) were selected using correlation strength and clinical plausibility of their association with a particular QLQ-C30 scale. Three change status groups were formed: deteriorated by one anchor category, improved by one anchor category, and no change. Patients with greater anchor changes were excluded. The mean change method was used to estimate MIDs for within-group change, and linear regression was used to estimate MIDs for between-group differences in change over time. For a given QLQ-C30 scale, MID estimates from multiple anchors were triangulated to a single value via a correlation-based weighted average.

Results: MIDs varied by QLQ-C30 scale, direction (improvement vs deterioration), and anchor. MIDs for within-group change ranged from 5 to 14 points (improvement) and -14 to -4 points (deterioration), and MIDs for between-group change over time ranged from 4 to 11 points and from -18 to -4 points. Correlation-weighted MIDs for most QLQ-C30 scales ranged from 4 to 10 points in absolute values.

Conclusions: Our findings aid interpretation of changes in EORTC QLQ-C30 scores over time, both within and between groups, and for performing more accurate sample size calculations for clinical trials in advanced breast cancer.
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http://dx.doi.org/10.1093/jncics/pkz037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050000PMC
September 2019

Health-related quality of life as an endpoint in oncology phase I trials: a systematic review.

BMC Cancer 2019 Apr 16;19(1):361. Epub 2019 Apr 16.

Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, University Hospital of Besançon, Besançon, France.

Background: Phase I trials aim to identify the recommended dose for further development. Health-related quality of life (HRQoL) could be a complement to the usual National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale to detect adverse events and define the doses. The objective of this study is to review the phase I in oncology which used HRQoL as endpoint.

Methods: A search in PubMed database identified phase I trials in oncology with HRQoL as endpoint, published between January 2012 to May 2016. Hematological and pediatric phase I were excluded.

Results: A total of 1333 phase I were identified and 15 trials were identified with HRQoL as endpoint (1.1%). The European Organisation for Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was the most frequently used instrument: 5 studies (33.3%). The targeted dimensions of HRQoL and the minimal clinically important difference were prespecified in 1 study (6.7%) and 2 studies (13.3%), respectively. Twelve studies (80%) described the statistical approach to analyze HRQoL data. Eight studies used the mean change from baseline (60%) to analyse longitudinal HRQoL data, two the mean score at certain times (13.3%), one the linear mixed model for repeated measures (6.7%), one the time to HRQoL score deterioration (6.7%), one percentage of patient-reported symptoms (6.7%). None of the studies used HRQoL to determine the recommended doses.

Conclusion: Few phase I studies used HRQoL as endpoint and among studies with HRQoL as endpoint, the methodology of HRQoL measurement and statistical analysis was heterogeneous. HRQoL. endpoint not used for assessing the recommended phase II doses.
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http://dx.doi.org/10.1186/s12885-019-5579-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469065PMC
April 2019

Clinical Relevance of Routine Monitoring of Patient-reported Outcomes Clinician-reported Outcomes in Oncology.

In Vivo 2019 Jan-Feb;33(1):17-21

Department of Medical Oncology, University Hospital of Nimes, Nimes, France.

The National Cancer Institute Common Terminology Criteria for Adverse Events classification is the standard classification used by the physicians in oncology for reporting adverse events. This classification has evolved over the last years according to the emergence of new therapies. Reporting symptoms, quality of life (QoL) and toxicities via patient-reported outcomes (PROs) in clinical practice is not yet a standard of care, nevertheless many studies have been conducted recently to assess feasibility and impact of routine monitoring of PROs, which should enable for better management of toxicities and earlier detection of disease progression in a more patient-centered health care delivery system. The aim of this article was to discuss the advantages and limitations of both approaches, clinicians-reported outcomes and PROs. Growing evidence supports that the routine collection of PROs leads to improvement of QoL and overall survival of cancer patients.
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http://dx.doi.org/10.21873/invivo.11433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364064PMC
April 2019

An international survey-based study on colorectal cancer pathology reporting-guidelines versus local practice.

Virchows Arch 2018 Dec 26;473(6):697-708. Epub 2018 Sep 26.

European Society of Pathology, Rue Bara 6, 1070, Brussels, Belgium.

Different guidelines for colorectal cancer (CRC) pathology reporting have been published. We aimed to identify differences between publicly available CRC reporting guidelines and to survey pathologists from different countries to establish the degree of guideline implementation in local routine practice. We compared all core and non-core items of CRC reporting guidelines to identify discrepancies. We then created a survey, which was sent out to 782 pathologists practicing in 30 different countries. It included questions on the demographics of the reporting pathologist as well as resection specimen handling and microscopic evaluation, grading, staging, and additional techniques, such as immunohistochemistry or molecular pathology. First, core and non-core items of five national CRC reporting guidelines were compared and 12 items were found to differ. Different items are considered core or non-core by different guidelines and more than one TNM staging edition was applied across guidelines. The survey was completed by 143 pathologists from 30 countries. We identified differences between local practice and guidelines with potential clinical impact, e.g., tumor budding was never reported by 28.7% of responders, although it has prognostic value for survival in stage II CRC. This is the first international study comparing CRC pathology reporting guidelines with real-world local practices. There are differences in CRC pathology reporting guidelines and in guideline implementation into local practice, both with potential impact on patient care. Harmonization of datasets, use of templates, and audits of local pathology practice are needed to ensure best possible quality of CRC pathology reporting.
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http://dx.doi.org/10.1007/s00428-018-2457-3DOI Listing
December 2018

[Impacts of routine patient-reported-outcomes monitoring in oncology].

Bull Cancer 2018 Sep 20;105(9):847-848. Epub 2018 Jul 20.

CHU de Nîmes, service d'oncologie médicale, 4, rue du Professeur-Robert-Debré, 30029 Nîmes, France; Université de Montpellier, 163, rue Auguste-Broussonnet, 34090 Montpellier, France; Université de Montpellier, Institut de recherche en cancérologie de Montpellier, Inserm U1194, Montpellier, France.

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http://dx.doi.org/10.1016/j.bulcan.2018.06.010DOI Listing
September 2018

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study.

Eur J Cancer 2018 08 15;99:49-57. Epub 2018 Jun 15.

EORTC Headquarters, Brussels, Belgium.

Background: Dose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy.

Methods: Survival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model.

Results: 13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m, and 5.3% had both a BMI ≥ 30 kg/m and a body surface area (BSA) ≥2 m. Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m and 32.4% with BMI ≥ 30 kg/m and BSA ≥ 2 m, respectively. In patients with BMI ≥ 30 kg/m, multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43-1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m and BSA ≥ 2 m, multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27-0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28-1.01; p = 0.052). This group comprised predominantly of men.

Conclusions: Data support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer.
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http://dx.doi.org/10.1016/j.ejca.2018.05.004DOI Listing
August 2018

Enterocolitis in Patients with Cancer Treated with Docetaxel.

Anticancer Res 2018 04;38(4):2443-2446

Department of Medical Oncology, University Hospital of Besançon, Besançon, France.

Background: Enterocolitis is a rare, but serious gastrointestinal complication associated with docetaxel-based chemotherapy in patients with cancer. The incidence, clinical presentation and outcome of enterocolitis in patients with cancer treated with docetaxel-based chemotherapy was assessed in this study Patients and Methods: All patients treated with docetaxel for cancer between January 2010 and December 2014 at the University Hospital of Besançon were identified and their medical records reviewed.

Results: During this period, 1,227 patients received docetaxel chemotherapy and gastrointestinal events occurred in 381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal events was associated with a higher dose of docetaxel (≥75 mg/m) (odds ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65 (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%) patients, respectively; 54 patients (14.2%) were hospitalized. Computed tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients presented radiological signs of enterocolitis. Three deaths (0.8%) related to enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120 patients (31.5%).

Conclusion: Gastrointestinal events in patients treated with docetaxel may be a potential sign of fatal enterocolitis and require particular attention. Dose reduction at the first cycle may reduce the risk of such events.
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http://dx.doi.org/10.21873/anticanres.12497DOI Listing
April 2018

Follow-up of patients with localized breast cancer and first indicators of advanced breast cancer recurrence: A retrospective study.

Breast 2017 Aug 12;34:53-57. Epub 2017 May 12.

University Hospital of Besançon, Department of Medical Oncology, France; University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit, France. Electronic address:

We conducted a retrospective study to assess the follow-up of patients with localized breast cancer and the first indicators of advanced breast cancer recurrence. All patients with advanced breast cancer recurrence treated between January 2010 and June 2016 in our institution were registered. Among these patients, 303 patients initially treated for early breast cancer with curative intent were identified. After initial curative treatment, follow-up involved the oncologist, the general practitioner and the gynecologist in 68.0%, 48.9% and 19.1% of cases, respectively. The median DFI was 4 years for luminal A, 3.8 years for luminal B, 3.7 years for HER2-positive and 1.5 years for TNBC (p = 0.07). Breast cancer tumor marker was prescribed for 164 patients (54.1%). No difference in terms of follow-up was observed according to the molecular subtype. Symptoms were the primary indicator of relapse for 143 patients (47.2%). Breast cancer recurrence was discovered by CA 15.3 elevation in 57 patients (18.8%) and by CAE elevation in 3 patients (1%). The rate of relapse diagnosed by elevation of CA 15.3 or CAE was not statistically associated with the molecular subtype (p = 0.65). Luminal A cases showed a significantly higher rate of bone metastases (p = 0.0003). TNBC cases showed a significantly higher rate of local recurrence (p = 0.002) and a borderline statistical significant higher rate of lung/pleural metastases (p = 0.07). Follow-up recommendations could be adapted in clinical practice according to the molecular subtype. General practitioners should be more involved by the specialists in breast cancer follow-up.
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http://dx.doi.org/10.1016/j.breast.2017.05.005DOI Listing
August 2017

Surrogate endpoints for overall survival in lung cancer trials: a review.

Expert Rev Anticancer Ther 2017 May 12;17(5):447-454. Epub 2017 Apr 12.

a Methodology and Quality of Life in Oncology Unit , University Hospital of Besançon , Besançon , France.

Introduction: Intermediate endpoints are often used as primary endpoints instead of overall survival (OS) in lung cancer trials but they are not systematically validated as surrogate endpoints for OS. Areas covered: The aim of the study was to review the studies which assessed potential surrogate endpoints for OS in lung cancer trials. Expert commentary: Twenty studies were identified. In operable non-small cell lung cancer (NSCLC) (adjuvant trials) and locally advanced NSCLC (radiotherapy trials), one individual-patient data meta-analysis found a high correlation of disease-free survival (DFS) and progression-free survival (PFS) with OS at patient and trial level. In trials of adjuvant chemotherapy, correlation between disease-free survival DFS and OS were 0.83 at the individual level (95% CI 0.83-0.83) and 0.92 at trial level (95% CI 0.88-0.95). In locally advanced disease, correlation between PFS and OS was 0.77 to 0.85 at the individual level, and 0.89 to 0.97 at trial level. This study provides a 'proof' of the surrogacy of PFS and DFS on OS according to the IQWiG framework and the surrogacy of PFS and DFS on OS was classified level 2 according to Fleming hierarchy. In all the other setting, no endpoint was judged to be valid surrogate for OS.
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http://dx.doi.org/10.1080/14737140.2017.1316196DOI Listing
May 2017

Reply to Sorscher S.

Breast 2017 06 23;33:203. Epub 2016 Dec 23.

University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit (INSERM UMR 1098), Besançon, France; The French National Platform Quality of Life and Cancer, Besançon, France.

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http://dx.doi.org/10.1016/j.breast.2016.12.005DOI Listing
June 2017

Time-to-event endpoints in operable non-small-cell lung cancer randomized clinical trials.

Expert Rev Anticancer Ther 2017 Feb 23;17(2):167-173. Epub 2016 Dec 23.

a Methodology and Quality of Life in Oncology Unit , University Hospital of Besançon , Besançon , France.

Introduction: No guideline for time-to-event endpoints (TTEE) definitions in lung cancer trials exists. Areas covered: The aim of the study was to evaluate the reporting of TTEE in operable non-small-cell lung cancer randomized clinical trials. Expert commentary: Sixty-two TTEE were recorded. In the Methods section, using four key points to define TTEE we observed that the 'starting point', 'events', 'information on censoring', 'assessment of events' were clearly defined for 43 (69.4%), 34 (54.8%), 6 (9.7%), 33 (53.2%) endpoints respectively. In the results section, using five key points, we observed that the 'Kaplan-Meier estimation', 'estimation of effect size', 'precision (confidence interval)', 'number of events', 'number of patients at risk', 'multivariate analysis' were clearly identified for 46 (74.2%), 31 (50%), 30 (48.4%), 37 (59.7%), 28 (45.2%), and 17 (27.4%) endpoints, respectively. A majority of articles failed to provide a complete reporting of TTEE. Guidelines for TTEE is warranted.
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http://dx.doi.org/10.1080/14737140.2016.1271718DOI Listing
February 2017

Docetaxel, Cisplatin, and 5-Fluorouracil as perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma.

Cancer Med 2016 11 11;5(11):3085-3093. Epub 2016 Oct 11.

Department of Medical Oncology, University Hospital of Besançon, Besançon, France.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) significantly improved overall survival in metastatic gastroesophageal adenocarcinoma (GEA). The aim of this study was to assess efficacy of DCF regimen as perioperative chemotherapy compared with surgery alone in patients with resectable GEA. We identified 789 patients who underwent surgery alone and 62 patients who received at least one cycle of DCF regimen consisting of docetaxel (75 mg/m on day 1), cisplatin (75 mg/m on day 1), and 5-fluorouracil (750 mg/m /day on continuous perfusion on days 1 to 5), every 3 weeks. Overall survival was compared using Cox proportional hazards regression model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis. In Cox multivariate analysis weighted by IPTW, DCF group was associated with favorable overall survival (OS) compared with the surgery group (HR = 0.59; 95% CI, 0.45-0.78; P = 0.0003). For the matched-pair analysis (comparing 41 patients for each group with the same baseline characteristics), median OS was 22 months and 57 months for the surgery group and DCF group, respectively (log-rank P = 0.0011). In Cox multivariate analysis, DCF group was associated with favorable OS compared with the surgery group (HR = 0.29; 95% IC, 0.14-0.64; P = 0.0019). In the matched-pair population, major complications (Dindo-Clavien grade 3-5) arose in six patients (14.63%) in the DCF group and seven patients (17.07%) in the surgery group (P = 1). Perioperative DCF chemotherapy is superior to surgery alone in terms of OS. A randomized phase III trial should compare DCF to standard perioperative regimens.
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http://dx.doi.org/10.1002/cam4.885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119963PMC
November 2016

Reply to B. Kurland et al.

J Clin Oncol 2016 12 31;34(36):4450-4451. Epub 2016 Oct 31.

Franck Bonnetain, University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit; and The French National Platform Quality of Life and Cancer; Institut National de la Santé et de la Recherche Médicale UMR 1098, Besançon France; Fabio Efficace, Data Center and Health Outcomes Research Unit, Italian Group for Adult Hematologic Diseases, Rome, Italy; Frédéric Fiteni, University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit, Besançon, France; and Amélie Anota, University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit; and The French National Platform Quality of Life and Cancer; Institut National de la Santé et de la Recherche Médicale UMR 1098, Besançon, France.

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http://dx.doi.org/10.1200/JCO.2016.69.6690DOI Listing
December 2016

Surrogate end points for overall survival in breast cancer trials: A review.

Breast 2016 Oct 9;29:44-8. Epub 2016 Jul 9.

University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit, Besançon, France; University Hospital of Besançon, Department of Medical Oncology, Besançon, France; The French National Clinical Research Platform Quality of Life and Cancer, Besançon, France.

Our aim was to review the studies which assessed potential surrogate endpoints for overall survival (OS) in breast cancer trials. A Literature search in PubMed database of studies which assessed potential surrogate endpoints for OS in breast cancer trials was conducted. The surrogacy was assessed with the German institute of Quality and efficiency in Health Care's (IWQiG) framework and the Fleming hierarchy. Thirteen studies were identified. At the neoadjuvant setting, two individual patient data (IPD) meta-analyses and one aggregate data meta-analysis assessing surrogacy of pathological complete response (PCR) were identified. Trial-level association was calculated in one study and the squared correlation was 0.24. Therefore PCR was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the adjuvant setting, one meta-analysis on aggregate data was identified. 2-year DFS was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the metastatic setting, six meta-analyses based on aggregate data, three IPD meta-analyses and one retrospective study were identified. Within the IPD meta-analyses, at the trial-level association the squared correlation between the potential surrogates and OS ranged from 0.10 to 0.57 and no endpoint was judged to be valid surrogate for OS at the metastatic setting. The level of evidence available supporting a relationship between OS and potential surrogate endpoints in breast cancer trials is low.
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http://dx.doi.org/10.1016/j.breast.2016.06.005DOI Listing
October 2016

Health-related quality of life in elderly patients with advanced non-small cell lung cancer comparing carboplatin and weekly paclitaxel doublet chemotherapy with monotherapy.

Eur Respir J 2016 09 23;48(3):861-72. Epub 2016 Jun 23.

Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France Chest Disease Dept, University Hospital of Besançon, Besançon, France.

In the Intergroupe Francophone de Cancérologie Thoracique 0501 trial the carboplatin-paclitaxel chemotherapy increased toxicity (most frequent, decreased neutrophil count, asthenia). We longitudinally compared health-related quality of life (HRQoL) of the two treatment arms.In total, 451 patients aged 70-89 years with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive carboplatin plus paclitaxel or vinorelbine or gemcitabine. HRQoL was assessed by means of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline, week 6 and week 18.Using a five-point decrease as the minimal clinically important difference, patients treated with the chemotherapy doublet exhibited a significant longer time until definitive deterioration (TUDD) for two HRQoL dimensions: physical functioning (median TUDD: 2.04 for the doublet versus 1.71 months for monotherapy; log-rank p=0.01) and nausea and vomiting (median: not reached versus 4.83, respectively; log-rank p=0.046). Cox multivariate analysis revealed the carboplatin and paclitaxel arm to be independently associated with longer TUDD for these two HRQoL dimensions. In addition, TUDD didn't significantly differ between the two arms for all the other HRQoL dimensions.The chemotherapy doublet did not reduce TUDD in elderly patients with advanced NSCLC. Moreover, TUDD was prolonged for two HRQoL dimensions, namely physical functioning and nausea and vomiting.
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http://dx.doi.org/10.1183/13993003.01695-2015DOI Listing
September 2016

Statistical Challenges in the Analysis of Health-Related Quality of Life in Cancer Clinical Trials.

J Clin Oncol 2016 06 18;34(16):1953-6. Epub 2016 Apr 18.

Franck Bonnetain, Frédéric Fiteni, and Amélie Anota, University Hospital of Besançon; Franck Bonnetain, Frédéric Fiteni, and Amélie Anota, INSERM U1098, University of Franche-Comté; Franck Bonnetain and Amélie Anota, The French National Platform of Quality of Life and Cancer, Besançon, France; and Fabio Efficace, Italian Group for Adult Hematologic Diseases, Rome, Italy.

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http://dx.doi.org/10.1200/JCO.2014.56.7974DOI Listing
June 2016

Methodology of health-related quality of life analysis in phase III advanced non-small-cell lung cancer clinical trials: a critical review.

BMC Cancer 2016 Feb 18;16:122. Epub 2016 Feb 18.

Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.

Background: Health-related quality of life (HRQoL) is recognized as a component endpoint for cancer therapy approvals. The aim of this review was to evaluate the methodology of HRQoL analysis and reporting in phase III clinical trials of first-line chemotherapy in advanced non-small cell lung cancers (NSCLC).

Methods: A search in MEDLINE databases identified phase III clinical trials in first-line chemotherapy for advanced NSCLC, published between January 2008 to December 2014. Two authors independently extracted information using predefined data abstraction forms.

Results: A total of 55 phase III advanced NSCLC trials were identified. HRQoL was declared as an endpoint in 27 studies (49%). Among these 27 studies, The EORTC questionnaire Quality of Life Questionnaire C30 was used in 13 (48%) of the studies and The Functional Assessment of Cancer Therapy-General was used in 12 (44%) trials. The targeted dimensions of HRQoL, the minimal clinically important difference and the statistical approaches for dealing with missing data were clearly specified in 13 (48.1%), 9 (33.3%) and 5 (18.5%) studies, respectively. The most frequent statistical methods for HRQoL analysis were: the mean change from baseline (33.3%), the linear mixed model for repeated measures (22.2%) and time to HRQoL score deterioration (18.5%). For each targeted dimension, the results for each group, the estimated effect size and its precision were clearly reported in 4 studies (14.8%), not clearly reported in 11 studies (40.7%) and not reported at all in 12 studies (44.4%).

Conclusions: This review demonstrated the weakness and the heterogeneity of the measurement, analysis, and reporting of HRQoL in phase III advanced NSCLC trials. Precise and uniform recommendations are needed to compare HRQoL results across publications and to provide understandable messages for patients and clinicians.
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http://dx.doi.org/10.1186/s12885-016-2152-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758022PMC
February 2016

Carboplatin-etoposide combination chemotherapy in metastatic castration-resistant prostate cancer: A retrospective study.

Mol Clin Oncol 2015 Nov 31;3(6):1208-1212. Epub 2015 Aug 31.

Department of Medical Oncology, University Hospital of Besançon, 25030 Besançon, France; Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, 25030 Besançon, France.

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differentiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolerability of the carboplatin-etoposide regimen in metastatic castration-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin [area under the curve (AUC)=5] and etoposide (100 mg/m intravenous infusion on days 1-3 or 75 mg orally/day for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months [95% confidence interval (CI): 1.9-4.2] and the median overall survival (OS) was 8.1 months (95% CI: 4.06-12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocytopenia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treatment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospective investigation to confirm its efficacy.
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http://dx.doi.org/10.3892/mco.2015.628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665308PMC
November 2015

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients.

Eur J Cancer 2016 Jan 10;52:120-8. Epub 2015 Dec 10.

Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France; University Hospital of Besançon, Pneumology Department, France.

Background: We investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC).

Methods: We included 451 NSCLC patients aged 70-89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS.

Results: Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980-0.992). We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤ GH ≤ 67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001). In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49-1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54-0.96; P=0.023 and HR: 0.50; 95% CI: 0.30-0.84; P=0.0089, respectively).

Conclusion: This study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.
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http://dx.doi.org/10.1016/j.ejca.2015.10.004DOI Listing
January 2016

Health-related quality-of-life as co-primary endpoint in randomized clinical trials in oncology.

Expert Rev Anticancer Ther 2015 31;15(8):885-91. Epub 2015 May 31.

University Hospital of Besançon, Methodology and Quality of Life in Oncology Unit, Besançon, France.

Overall survival (OS) has been considered as the most relevant primary endpoint but trials using OS often require large numbers of patients and long-term follow-up. Therefore composite endpoints, which are assessed earlier, are frequently used as primary endpoint but suffer from important limitations specially a lack of validation as surrogate of OS. Therefore, Health-related quality of life (HRQoL) could be considered as an outcome to judge efficacy of a treatment. An alternative approach would be to combine HRQoL with composite endpoints as co-primary endpoint to ensure a clinical benefit for patients of a new therapy. The decision rules of such design, the procedure to control the Type I error and the determination of sample size remain questions to debate. Here, we discusses HRQoL as co-primary endpoints in randomized clinical trials in oncology and provide some solutions to promote such design.
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http://dx.doi.org/10.1586/14737140.2015.1047768DOI Listing
April 2016

The impact of taxane-based preoperative chemotherapy in gastroesophageal signet ring cell adenocarcinomas.

J Hematol Oncol 2015 May 15;8:52. Epub 2015 May 15.

Department of Medical Oncology, University Hospital of Besancon, 3 Boulevard Alexander Fleming, Besancon, F-25030, France.

The benefit of preoperative chemotherapy in resectable gastroesophageal adenocarcinomas was not observed in signet ring cell subtype. However, the potential interest of taxane-based preoperative chemotherapy on this subtype is still an unresolved issue. Nineteen patients with localized signet ring cell adenocarcinomas received taxane-based regimens, and 17 patients underwent surgery. Complete resection was achieved in 80 %, and median overall survival was 40.8 months (95 % confidence interval (CI), 20.2-not reached). Even though one patient achieved a complete pathological response, seven patients had an upstaging of their tumors at surgery. The potential benefits of taxane-based chemotherapy seem to be limited to a reduced number of patients.
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http://dx.doi.org/10.1186/s13045-015-0148-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440289PMC
May 2015

[Health-related quality of life in phase III cancer clinical trials: from questionnaire administration to statistical analysis].

Bull Cancer 2015 Apr 21;102(4):360-6. Epub 2015 Mar 21.

CHU de Besançon, unité de méthodologie en qualité de vie et cancérologie, 25000 Besançon, France; Université de Franche-Comté, EA 3181, 25000 Besançon, France; Plateforme de qualité de vie et cancer, 25000 Besançon, France; EORTC QOL groupe, Bruxelles, Belgique.

Endpoints refer to clinical and biological measurements that assess efficacy of therapeutic strategies. As the American Society of Clinical Oncology states, active treatment in cancer is generally undertaken with the goal of providing improved quantity and/or quality of patient survival. Health-related quality of life (HRQoL) reflects the patient-perceived evaluation of one's health, including physical, emotional, and social dimensions as well as symptoms due to disease or treatment. HRQoL is recognized as a component endpoint for cancer therapy approvals by the American Society of Clinical Oncology and the FDA. Many self-completion HRQoL questionnaires have been developed and validated. Two main statistical methods have been developed to longitudinally analyze HRQoL. The first is the linear mixed model for repeated measure (LMM). The second is a survival approach, which estimates the time to HRQoL deterioration. However, there is no guideline for methods of analyzing and reporting longitudinal changes in HRQoL scores. Moreover, HRQoL could also be combined with other endpoints like progression-free survival as co-primary endpoint, but the use of co-primary endpoints in cancer clinical trials is a new approach and methodological researches must be pursued to promote such designs.
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http://dx.doi.org/10.1016/j.bulcan.2015.02.014DOI Listing
April 2015

Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy.

BMC Gastroenterol 2014 Aug 13;14:143. Epub 2014 Aug 13.

Department of Medical Oncology, Jean Minjoz University Teaching Hospital, 3 Boulevard Alexander Fleming, Besançon F-25030, France.

Background: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts.We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy.

Methods: Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy.

Results: With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare.With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%).At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5).

Conclusions: One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP.At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy.
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http://dx.doi.org/10.1186/1471-230X-14-143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236575PMC
August 2014

Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review.

Cancer Med 2014 Dec 11;3(6):1502-11. Epub 2014 Aug 11.

Department of Medical Oncology, University Hospital of Besançon, Besançon, France; Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France.

Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity.
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http://dx.doi.org/10.1002/cam4.299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298376PMC
December 2014

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: impact of institutions.

Breast 2014 Apr 22;23(2):165-9. Epub 2013 Dec 22.

Department of Medical Oncology, Besançon University Hospital, Besançon, France. Electronic address:

Purpose: Trastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given.

Patients & Methods: All patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS).

Results: Among 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2-89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64-0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59-0.95; p = 0.02).

Conclusion: Exposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.
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http://dx.doi.org/10.1016/j.breast.2013.12.003DOI Listing
April 2014

Time to health-related quality of life score deterioration as a modality of longitudinal analysis for health-related quality of life studies in oncology: do we need RECIST for quality of life to achieve standardization?

Qual Life Res 2015 Jan 26;24(1):5-18. Epub 2013 Nov 26.

Quality of Life in Oncology Clinical Research Platform, Besançon, France,

Purpose: Longitudinal analysis of health-related quality of life (HRQoL) remains unstandardized and compromises comparison of results between trials. In oncology, despite available statistical approaches, results are poorly used to change standards of care, mainly due to lack of standardization and the ability to propose clinical meaningful results. In this context, the time to deterioration (TTD) has been proposed as a modality of longitudinal HRQoL analysis for cancer patients. As for tumor response and progression, we propose to develop RECIST criteria for HRQoL.

Methods: Several definitions of TTD are investigated in this paper. We applied this approach in early breast cancer and metastatic pancreatic cancer with a 5-point minimal clinically important difference. In breast cancer, TTD was defined as compared to the baseline score or to the best previous score. In pancreatic cancer (arm 1: gemcitabine with FOLFIRI.3, arm 2: gemcitabine alone), the time until definitive deterioration (TUDD) was investigated with or without death as event.

Results: In the breast cancer study, 381 women were included. The median TTD was influenced by the choice of the reference score. In pancreatic cancer study, 98 patients were enrolled. Patients in Arm 1 presented longer TUDD than those in Arm 2 for most of HRQoL scores. Results of TUDD were slightly different according to the definition of deterioration applied.

Conclusion: Currently, the international ARCAD group supports the idea of developing RECIST for HRQoL in pancreatic and colorectal cancer with liver metastasis, with a view to using HRQoL as a co-primary endpoint along with a tumor parameter.
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http://dx.doi.org/10.1007/s11136-013-0583-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282717PMC
January 2015

First-line trastuzumab plus taxane-based chemotherapy for metastatic breast cancer: cost-minimization analysis.

J Oncol Pharm Pract 2014 Oct 24;20(5):362-8. Epub 2013 Oct 24.

Department of Pharmacy, University Teaching Hospital of Besançon, France INSERM U645 EA-2284 IFR-133, University of Franche-Comté, Besançon, France.

Aim: To carry out a cost-minimization analysis including a comparison of the costs arising from first-line treatment by trastuzumab plus docetaxel versus trastuzumab plus paclitaxel in patients with metastatic breast cancer.

Methods: All consecutive patients with human epidermal growth receptor 2-postive metastatic breast cancer who were treated at Besançon University Hospital and Saint Vincent private hospital between 2001 and 2010 by first-line therapy containing trastuzumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization, and healthcare travel.

Results: Progression-free survival difference between the two treatments was not significant (p = 0.65). First-line treatment by trastuzumab plus taxane was estimated at approximately €68,000 (p = 0.74). The drug costs represented around 70-75% of the total cost, mainly related to the use of trastuzumab.

Conclusion: Our economic analysis shows that although the costs of the two trastuzumab plus taxane regimens are similar, they may contribute to the on-going debate about the availability and use of innovative chemotherapy drugs, in particular in human epidermal growth factor receptor 2-positive metastatic breast cancer with new therapies such as trastuzumab-DM1 and pertuzumab.
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http://dx.doi.org/10.1177/1078155213508440DOI Listing
October 2014