Publications by authors named "Melanie Dos Santos"

11 Publications

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Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial.

Cancer 2020 Dec 30;126(24):5328-5336. Epub 2020 Sep 30.

Clinical Research Department, Centre François Baclesse, Caen, France.

Background: There is no treatment for cancer-related cognitive impairment, an important adverse effect that negatively impacts quality of life (QOL). We conducted a 3-arm randomized controlled trial to evaluate the impact of computer-assisted cognitive rehabilitation (CR) on cognition, QOL, anxiety, and depression among cancer patients treated with chemotherapy.

Methods: Patients who reported cognitive complaints during or after completing chemotherapy were randomly assigned to 1 of 3 12-week CR programs: computer-assisted CR with a neuropsychologist (experimental group A), home cognitive self-exercises (active control group B), or phone follow-up (active control group C). Subjective cognition was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), objective cognition was assessed by neuropsychological tests, QOL was assessed by the FACT-General, and depression and anxiety were assessed by psychological tests. The primary endpoint was the proportion of patients with a 7-point improvement in the FACT-Cog perceived cognitive impairment (PCI) score.

Results: Among the 167 enrolled patients (median age, 51 years), group A had the highest proportion of patients with a 7-point PCI improvement (75%), followed by groups B (59%) and C (57%), but the difference was not statistically significant (P = .13). Compared with groups B and C, the mean difference in PCI score was significantly higher in group A (P = .02), with better perceived cognitive abilities (P < .01) and a significant improvement in working memory (P = .03). Group A reported higher QOL related to cognition (FACT-Cog QOL) (P = .01) and improvement in depression symptoms (P = .03).

Conclusions: These results suggest a benefit of a computer-based CR program in the management of cancer-related cognitive impairment and complaints.
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http://dx.doi.org/10.1002/cncr.33186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756299PMC
December 2020

Implantation of tissue expander prior to irradiation in the era of intensity modulated radiotherapy: impact on the management of patients with pelvic digestive cancers.

Int J Colorectal Dis 2020 Mar 18;35(3):559-564. Epub 2019 Dec 18.

Centre François Baclesse, Radiation oncology Department, 3 avenue du general Harris, 14000, Caen, France.

Purpose: Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient's overall treatment and may be no more necessary in the era of modern radiotherapy.

Material And Methods: This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers.

Results: Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51 months [3.7-115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3 months), requiring unusual induction chemotherapy.

Conclusion: Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy-V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.
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http://dx.doi.org/10.1007/s00384-019-03475-zDOI Listing
March 2020

Long-Term Fatigue and Cognitive Disorders in Breast Cancer Survivors.

Cancers (Basel) 2019 Nov 28;11(12). Epub 2019 Nov 28.

INSERM Unit 981, Gustave Roussy, 94800 Villejuif, France.

Survivors of early-stage breast cancer may report treatment-related side effects that persist for several years after the end of primary treatment. Among these, fatigue and cognitive disorders are frequent complaints and can negatively impact quality of life. Cancer-related fatigue is a very prevalent and distressing long-term side effect among breast cancer survivors that typically improves after completion of treatment, although many patients report severe fatigue several years post-treatment. Cognitive disorders are also common among survivors of breast cancer, especially if treated with chemotherapy. These symptoms are usually mild-to-moderate and often transient. Cognitive recovery is frequently observed within months or a few years after completion of chemotherapy or endocrine therapy. However, some breast cancer survivors may have persistent cognitive difficulties. Several types of interventions have proved to be beneficial in reducing cancer-related fatigue and cognitive difficulties. Most of these interventions for cancer-related fatigue are thought to be effective by reducing inflammation or disrupting pro-inflammatory circuits. Further studies are needed on cognitive management that has showed promising results. This narrative review summarizes the state of the art regarding long-term fatigue and cognitive disorders in patients with early breast cancer, describing prevalence, impact, pathophysiology, and risk factors, and focusing on available interventions.
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http://dx.doi.org/10.3390/cancers11121896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966680PMC
November 2019

Clinical periodontal conditions in individuals after bariatric surgery: a systematic review and meta-analysis.

Surg Obes Relat Dis 2019 10 17;15(10):1850-1859. Epub 2019 Jul 17.

School of Dentistry, University of Pernambuco, Camaragibe, Pernambuco, Brazil. Electronic address:

The aim of the present study was to perform a systematic review and meta-analysis to assess the influence of bariatric surgery on the clinical periodontal conditions in patients with obesity. This review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered at the International Prospective Registry of Systematic Reviews (CRD42018099313). A search was conducted by 2 investigators in the PubMed/MEDLINE, Web of Science, and Cochrane Library databases for relevant articles published up to May 2018. The inclusion criteria were randomized controlled trials, prospective and retrospective studies, observational studies, longitudinal studies, and cohort studies with at least 3 months of follow-up. No language restrictions were imposed. The exclusion criteria were studies that did not evaluate or report the periodontal measurements, cross-sectional studies (without follow-up after surgery), studies that performed periodontal treatment, and those with insufficient periodontal data. The meta-analysis was based on the Mantel-Haenszel method and inverse variance. The quantitative analysis revealed no statistically significant differences with regard to bleeding on probing (P = .9; mean deviation: -.70; confidence interval = -11.43 to 10.04) or probing pocket depth (P = .41; mean deviation: -.46; confidence interval = -1.55 to .63) before and after intervention. Clinical attachment loss showed a statistically significant difference (P = .0002; mean deviation: .18; confidence interval = .07-.30). It can be concluded that bariatric surgery does not influence bleeding on probing or probing pocket depth, but leads to a worsening of clinical attachment loss.
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http://dx.doi.org/10.1016/j.soard.2019.07.008DOI Listing
October 2019

Maximizing binary interactome mapping with a minimal number of assays.

Nat Commun 2019 08 29;10(1):3907. Epub 2019 Aug 29.

Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute (DFCI), 450 Brookline Avenue, Boston, MA, 02215, USA.

Complementary assays are required to comprehensively map complex biological entities such as genomes, proteomes and interactome networks. However, how various assays can be optimally combined to approach completeness while maintaining high precision often remains unclear. Here, we propose a framework for binary protein-protein interaction (PPI) mapping based on optimally combining assays and/or assay versions to maximize detection of true positive interactions, while avoiding detection of random protein pairs. We have engineered a novel NanoLuc two-hybrid (N2H) system that integrates 12 different versions, differing by protein expression systems and tagging configurations. The resulting union of N2H versions recovers as many PPIs as 10 distinct assays combined. Thus, to further improve PPI mapping, developing alternative versions of existing assays might be as productive as designing completely new assays. Our findings should be applicable to systematic mapping of other biological landscapes.
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http://dx.doi.org/10.1038/s41467-019-11809-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715725PMC
August 2019

Optimisation of chemotherapy prescription and preparation in an ambulatory unit: Validation of the OPTIMA program.

Eur J Cancer Care (Engl) 2019 May 20;28(3):e13015. Epub 2019 Feb 20.

Ambulatory Department, Centre François Baclesse, Caen, France.

Objective: We implemented the two-step OPTIMA program to anticipate chemotherapy prescription which aims to assess the discrepancy rate between anticipated and real prescription and its impact on waiting time and quality of care.

Methods: This prospective study included cancer patients receiving any intravenous chemotherapy. The OPTIMA program consists in a nurse phone call and a blood sample two days before the planned treatment. Collected information and biological results were used by a physician to issue a non-effective (step 1) or effective (step 2) anticipated prescription the day before the consultation. The real prescription was given as usual by another physician on the day of the consultation. Waiting time was collected, and patients' satisfaction with care was assessed with the OUT-PATSAT35 questionnaire.

Results: Respectively, 540 and 979 consultations (283 and 294 patients) were analysed in both steps. The discrepancy rate was 8.7% (step 1). In routine practice, the OPTIMA program (step 2) reduced patients' waiting time (median time 55 vs. 95 min, p < 0.001). A high general care satisfaction score was observed in both steps (80.7% and 80.2%).

Conclusions: This anticipation program demonstrated the accuracy of chemotherapy prescription, whatever the regimen and cancer site, and its impact on waiting time optimisation.
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http://dx.doi.org/10.1111/ecc.13015DOI Listing
May 2019

Impact of anxio-depressive symptoms and cognitive function on oral anticancer therapies adherence.

Support Care Cancer 2019 Sep 28;27(9):3573-3581. Epub 2019 Jan 28.

Clinical Research Department, Centre François Baclesse, 14000, Caen, France.

Purpose: Oral anticancer therapies have an important place in the therapeutic arsenal, but factors influencing adherence to oral treatment are poorly documented in oncology. The objective of this study was to assess the impact of anxio-depressive symptoms and cognitive functioning on oral medication adherence.

Methods: This prospective study included cancer patients initiating a first oral therapy. Before initiation of treatment, an assessment of depression, anxiety, and cognition was performed. Using self-report questionnaires, we collected information on socio-demographic conditions and the non-adherence at 1 (M1) and 3 months (M3) after the beginning of treatment.

Results: Among 129 patients enrolled, median age was 70 years and 81% of patients were treated for metastatic cancer. Before initiating treatment, 16% and 8% of patients presented respectively depression and anxiety symptoms. Global cognitive impairment was observed in 51% of patients. Ten percent of the patients were non-adherent at M1 and 13% at M3. Depression was strongly associated with non-adherence at M1 (P = 0.046) and M3 (P = 0.014), but not anxiety. Non-adherence was associated with lower working memory (P = 0.037) and digit memory (P = 0.018) at M1 and short-term memory (P = 0.04) at M3. Patients with more than eight co-medications were more often non-adherents (P = 0.055).

Conclusions: Non-adherence to oral anticancer therapies was mainly associated to depression. Focusing on depressive symptoms before initiation of oral anticancer therapy could help to identify patient profiles more likely to fail self-management. Working memory, digit memory, and short-term memory also seem to play a role in non-adherence. Further studies should include a more specific population, especially according to age.
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http://dx.doi.org/10.1007/s00520-019-4644-4DOI Listing
September 2019

Sexual Disorders of Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Antiangiogenic Therapies.

Clin Genitourin Cancer 2018 10 21;16(5):369-375.e1. Epub 2018 May 21.

U1086 INSERM-UCBN "Cancers & Préventions", Normandie Université, Caen, France; Departments of Clinical Research Unit, Centre François Baclesse, Caen, France; Department of Medical Oncology, Centre François Baclesse, Caen, France. Electronic address:

Background: Targeted therapies, in particular antiangiogenic therapies (AATs), have become the standard of treatment for metastatic renal cell carcinoma (mRCC). Although common adverse effects like fatigue have been well-established, sexual disorders induced by these treatments, although often reported, have been poorly evaluated. The aim of this study was to evaluate the impact of AATs on the sexual life of patients with mRCC and the relationships with quality of life (QoL), fatigue, and biologic parameters.

Patients And Methods: This longitudinal study included patients with mRCC on first- or second-line AATs. Sexuality was evaluated by the French version of Changes in Sexual Functioning Questionnaire short-Form (CSFQ); QoL and fatigue were measured by the Functional Assessment of Cancer Therapy General (FACT-G) and the Multidimensional Fatigue Inventory (MFI-20), respectively. Biologic parameters were also assessed.

Results: Among 75 patients included in the study, 39 agreed to respond to the sexual functioning questionnaire (CSFQ). At baseline, all patients had at least 1 sexual dysfunction. No relationship with QoL, fatigue, and biologic parameters was shown. After 3 months of treatment, a decrease in at least 1 sexual dimension was observed in 69% of patients. The most affected sexual dimensions were pleasure (34%) and desire/interest (38%). No significant relationship between sexual dysfunctions and biologic parameters was found. The percentage of non-participants (50%) and the absence of a control arm are the main limitations.

Discussion: Patients with mRCC exhibit sexual dysfunction that could be increased by AATs independently of the impact on fatigue and QoL. Further studies aiming to define the role of biologic parameters like inflammatory markers and thyroid parameters are warranted.

Conclusion: Sexual disorders induced or degraded by AAT are an independent side effect that should be taken into account in oncology supportive care departments.
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http://dx.doi.org/10.1016/j.clgc.2018.05.013DOI Listing
October 2018

Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs.

Sci Rep 2016 Sep 22;6:33763. Epub 2016 Sep 22.

Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, F-75015 Paris, France.

Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037575PMC
http://dx.doi.org/10.1038/srep33763DOI Listing
September 2016

Paraneoplastic leukemoid reaction in pancreatic cancer: A case report.

World J Gastrointest Oncol 2015 Oct;7(10):259-62

Mélanie Dos Santos, Karine Bouhier, Manh-Thong Dao, Department of Gastroenterology, CHU de Caen, 14000 Caen, France.

Paraneoplastic leukemoid reaction is a rare syndrome defined by a leukocyte count exceeding 50 Giga/Liter (G/L), mostly described with progressive lung or renal carcinoma. We report a case of a 68-year-old man with recurrent pancreatic carcinoma presenting a leukemoid reaction with a white blood cell count of 63.87 G/L without identified infectious, iatrogenic or hematologic causes. His overall condition quickly degraded and he died three weeks after the discovery of the leukemoid reaction. This is the first case in French literature of leukemoid reaction in a patient with pancreatic carcinoma with poor prognostic value.
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http://dx.doi.org/10.4251/wjgo.v7.i10.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606180PMC
October 2015

[Rapid detection of BCHE atypical variant (p.Asp70Gly) by high resolution melting curve analysis].

Ann Biol Clin (Paris) 2014 Sep-Oct;72(5):543-8

Hôpital d'instruction des armées Bégin, Fédération de biologie clinique, Saint Mandé, France.

Butyrylcholinesterase (BChE) deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium). Although many acquired conditions may affect BChE activity, BChE deficiency is mainly due to mutations in the BCHE gene (MIM 177400). Though close to 70 natural mutations have been documented in human BCHE, the atypical variant (rs1799807) is the most frequently involved in prolonged apnea. We describe an HRM method for the detection of this variant. Thirty-four patients with known genotype [5 wild-type (U/U), 12 heterozygous (U/A), 17 homozygous (A/A) - A: atypical allele of BCHE, U: usual allele of BCHE -] were screened with the HRM analysis. Within and between-run precision were also evaluated. In silico prediction of HRM curves was performed in order to evaluate the potential impact of the other SNPs described within the PCR product on the HRM diagnostic accuracy. HRM analysis for the BCHE atypical variant genotyping is a simple, rapid, sensitive and low cost method.
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http://dx.doi.org/10.1684/abc.2014.0994DOI Listing
November 2015