Publications by authors named "Elisabeth Daguenet"

26 Publications

  • Page 1 of 1

CDK 4/6 inhibitors combined with radiotherapy: A review of literature.

Clin Transl Radiat Oncol 2021 Jan 1;26:79-85. Epub 2020 Dec 1.

Department of Radiation Oncology, Lucien Neuwirth Cancer Institute, 108 bis avenue Albert Raimond, BP60008, 42271 Saint Priest en Jarez cedex, France.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) namely palbociclib, ribociclib and abemaciclib were granted approval by the European Medicines Agency (EMA) between 2017 and 2018. They are currently prescribed in combination with hormone therapy to treat hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Their combination with radiotherapy raises safety concerns as preclinical data enlightened their possible synergistic effect. Moreover, data about toxicity when combining CDK4/6i with radiotherapy are scarce. This review of literature focused on the use of CDK4/6i combined with radiotherapy. It aimed at listing every published data about such combination so as to understand its possible resulting toxicity in metastatic breast cancer.
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http://dx.doi.org/10.1016/j.ctro.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724290PMC
January 2021

Impact of COVID-19 Outbreak through Telemedicine Implementation on Data Reporting During Oncology Clinical Trials.

Cancer Invest 2021 Jan 10;39(1):15-20. Epub 2020 Dec 10.

Clinical Research Department, Lucien Neuwirth Cancer Institute, Saint Priest en Jarez, France.

Coronavirus disease outbreak has affected all aspect of clinical care including cancer clinical trials. To minimize exposure of frail cancer patients, an implementation of telemedicine was retained. The impact of this implementation on primary and secondary endpoints criteria of ongoing clinical trials was analyzed. Out of 128 oncology clinical trials, 25 (19%) had an implementation of teleconsultation. Poor data reporting induced mainly a bias on qualitative and descriptive primary endpoints than those assessing efficacy (80% 20%;  < 0.001). The integration of telemedicine and E-technologies in the medical practices and clinical trials must be designed and validated.
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http://dx.doi.org/10.1080/07357907.2020.1858311DOI Listing
January 2021

How to improve clinical research in a department of radiation oncology.

Bull Cancer 2020 Oct 17;107(10):991-998. Epub 2020 Sep 17.

Institut de Cancérologie Lucien Neuwirth, Department of Radiation Oncology, 108 bis, avenue Albert-Raimond, BP 60008, 42270 Saint-Priest-en-Jarez, France; University department of Research and Teaching, Institut de Cancérologie Lucien Neuwirth, 42270 Saint-Priest-en-Jarez, France; Laboratory of Molecular and Cellular Radiobiology, UMR CNRS5822/IN2P3, IPNL, PRISME, 69622 Villeurbanne, France. Electronic address:

Introduction: Radiation therapy is a core modality for cancer treatment. Around 40% of cancer cures include the use of radiotherapy, either as a single strategy or combined with other treatments. In the past decade, substantial technical advances and novel insights into radiobiological properties have considerably improved patients' outcomes. This study overviewed the landscape of clinical research at our radiotherapy department.

Methods: We surveyed our institutional database of clinical trials to collect information for completed or ongoing radiation therapy clinical trials, from 2005 to December 2017 at the Lucien Neuwirth cancer institute.

Results: A total of 31 clinical trials were undertaken during the study period, of which 4 studies (12.9%) were industry-sponsored and 3 studies (9.7%) were launched by our radiotherapy unit. The vast majority of clinical trials (83.9%) were dedicated to unique organ localization, especially urological cancer (prostate or bladder) (42%). We also observed a shift towards more phase II trials during the study period as well as a special focus on elderly population. Over the last decade, the number of included patients increased by a 5.3 fold input, with 135 inclusions before 2011 and 720 inclusions after 2011.

Discussion: This study provided an observational and comprehensive analysis of radiotherapy research. From a monocentric point-of-view, these results reflected the on-going progress of worldwide radiotherapy research. Based on a 13-years' experience, this study aimed at highlighting essential cues to ensure efficient and perennial research.
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http://dx.doi.org/10.1016/j.bulcan.2020.06.007DOI Listing
October 2020

Chronic fatigue in myelodysplastic syndromes: Looking beyond anemia.

Crit Rev Oncol Hematol 2020 Oct 27;154:103067. Epub 2020 Jul 27.

Univ Lyon, UJM-Saint-Etienne, Inter-University Laboratory of Human Movement Biology, EA 7424, F-42023, Saint-Etienne, France; Institut Universitaire de France (IUF), France.

Chronic fatigue is the most common and severe symptom in myelodysplastic syndromes (MDS) and has a strong negative association with health-related quality of life (HRQoL). Despite anemia being the most common objective manifestation of MDS, and the associated link between anemia and fatigue, evidence on treatments which temporarily mitigate anemia is equivocal regarding the effects on fatigue. Furthermore, previous work has found weak associations between anemia and chronic fatigue in MDS. As such, given that improving HRQoL is one of the primary treatment aims in MDS, further work is required to identify other potential contributors to chronic fatigue in these patients. In addition to anemia, MDS is associated with numerous other deviations in physiological homeostasis and has negative psychological consequences with links to chronic fatigue. Accordingly, the present review provides several potential aetiologic agents relevant to chronic fatigue in MDS which can be used to guide future research in this field.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103067DOI Listing
October 2020

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.

Br J Cancer 2020 08 25;123(3):339-348. Epub 2020 Jun 25.

Département de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France.

Radiotherapy is a pivotal component in the curative treatment of patients with localised cancer and isolated metastasis, as well as being used as a palliative strategy for patients with disseminated disease. The clinical efficacy of radiotherapy has traditionally been attributed to the local effects of ionising radiation, which induces cell death by directly and indirectly inducing DNA damage, but substantial work has uncovered an unexpected and dual relationship between tumour irradiation and the host immune system. In clinical practice, it is, therefore, tempting to tailor immunotherapies with radiotherapy in order to synergise innate and adaptive immunity against cancer cells, as well as to bypass immune tolerance and exhaustion, with the aim of facilitating tumour regression. However, our understanding of how radiation impacts on immune system activation is still in its early stages, and concerns and challenges regarding therapeutic applications still need to be overcome. With the increasing use of immunotherapy and its common combination with ionising radiation, this review briefly delineates current knowledge about the non-targeted effects of radiotherapy, and aims to provide insights, at the preclinical level, into the mechanisms that are involved with the potential to yield clinically relevant combinatorial approaches of radiotherapy and immunotherapy.
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http://dx.doi.org/10.1038/s41416-020-0942-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403362PMC
August 2020

To exploit the 5 'R' of radiobiology and unleash the 3 'E' of immunoediting: 'RE'-inventing the radiotherapy-immunotherapy combination.

Ther Adv Med Oncol 2020 8;12:1758835920913445. Epub 2020 May 8.

Department of Radiotherapy, Institut de Cancérologie Lucien Neuwirth, 108 bis, avenue Albert Raimond, BP 60008, Saint-Priest-en-Jarez, 42270, France.

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http://dx.doi.org/10.1177/1758835920913445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222228PMC
May 2020

[Proteinuria in multiple myeloma: Be careful to iatrogeny].

Bull Cancer 2020 Apr 13;107(4):519-520. Epub 2020 Mar 13.

Institut de cancérologie Lucien-Neuwirth, département d'hématologie clinique, 42270 Saint-Priest-en-Jarez, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.01.014DOI Listing
April 2020

FAK Deficiency in Bone Marrow Stromal Cells Alters Their Homeostasis and Drives Abnormal Proliferation and Differentiation of Haematopoietic Stem Cells.

Cells 2020 03 6;9(3). Epub 2020 Mar 6.

Laboratoire d'Hématologie, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex, France.

Emerging evidence indicates that in myelodysplastic syndromes (MDS), the bone marrow (BM) microenvironment may also contribute to the ineffective, malignant haematopoiesis in addition to the intrinsic abnormalities of haematopoietic stem precursor cells (HSPCs). The BM microenvironment influences malignant haematopoiesis through indirect mechanisms, but the processes by which the BM microenvironment directly contributes to MDS initiation and progression have not yet been elucidated. Our previous data showed that BM-derived stromal cells (BMSCs) from MDS patients have an abnormal expression of focal adhesion kinase (FAK). In this study, we characterise the morpho-phenotypic features and the functional alterations of BMSCs from MDS patients and in FAK knock-downed HS-5 cells. The decreased expression of FAK or its phosphorylated form in BMSCs from low-risk (LR) MDS directly correlates with BMSCs' functional deficiency and is associated with a reduced level of haemoglobin. The downregulation of FAK in HS-5 cells alters their morphology, proliferation, and differentiation capabilities and impairs the expression of several adhesion molecules. In addition, we examine the CD34+ healthy donor (HD)-derived HSPCs' properties when co-cultured with FAK-deficient BMSCs. Both abnormal proliferation and the impaired erythroid differentiation capacity of HD-HSPCs were observed. Together, these results demonstrate that stromal adhesion mechanisms mediated by FAK are crucial for regulating HSPCs' homeostasis.
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http://dx.doi.org/10.3390/cells9030646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140540PMC
March 2020

Art Therapy Sessions for Cancer Patients: A Single-Centre Experience.

Oncology 2020 11;98(4):216-221. Epub 2020 Feb 11.

Department of Supportive Care in Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France,

Introduction: Cancer and anti-cancer therapies are often associated with pain, loss of self-worth, anxiety, and depression. Alternative therapies such as art therapy are available to improve patients' quality of life, by reducing asthenia, depression, anxiety and pain.

Objective: The aim of this study was to assess the effectiveness of art therapy, namely theatre and plastic art workshops, on well-being and quality of life of participants in the Lucien Neuwirth Cancer Institute.

Methods: A prospective study was conducted at the Lucien Neuwirth Cancer Institute (France), between April 2018 and July 2018. Cancer patients followed at the Institute have been asked to participate in 10 2-h sessions, once a week, based on theatre and plastic art workshops. Self-report questionnaires were used to evaluate both psychological and quality of life domains, but also satisfaction and well-being, before (pre-test) and after the last session (early post-test), as well as 1-month post-experimentation (late post-test).

Results: Among the 14 patients who were enroled, the QLQ-C30 questionnaire revealed a pre-test median score of 50.0, an early post-test score of 51.5, and the late post-test revealed a score of 48.0. The anxiety test revealed median scores of 8.0 (pre-test), 6.0 (early post-test) and 6.0 (late post-test), respectively. The depression test reported median scores of 4.0 (pre-test), 5.0 (early post-test) and 6.0 (late post-test), respectively. The median well-being score difference observed between the beginning and the end of sessions is +2.13. The minimum satisfaction score observed is 3.50 out of 10, and the maximum is 10 out of 10. The median is between 7.00 and 10.00.

Conclusions: Art therapy sessions had an impact on patients' welfare. We also reported a trend towards amelioration of quality of life that could probably be confirmed in a larger population, and potentially with a different methodology.
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http://dx.doi.org/10.1159/000504448DOI Listing
April 2020

Chemoradiation and granulocyte-colony or granulocyte macrophage-colony stimulating factors (G-CSF or GM-CSF): time to think out of the box?

Br J Radiol 2020 May 4;93(1109):20190147. Epub 2020 Feb 4.

Department of Radiotherapy, Lucien Neuwirth Cancer Institute, Saint-Priest en Jarez, France.

Concerns have been raised about potential toxic interactions when colony-stimulating factors (CSFs) and chemoradiation are concurrently performed. In 2006, the ASCO guidelines advised against their concomitant use. Nevertheless, with the development of modern radiotherapy techniques and supportive care, the therapeutic index of combined chemotherapy, radiotherapy, and CSFs is worth reassessing. Recent clinical trials testing chemoradiation in lung cancer let investigators free to decide the use of concomitant CSFs or not. No abnormal infield event was reported after the use of modern radiotherapy techniques and concomitant chemotherapy regimens. These elements call for further investigation to set new recommendations in favour of the association of chemoradiation and CSFs. Moreover, radiotherapy could induce anticancer systemic effects mediated by the immune system and . With combined CSFs, this effect was reinforced in preclinical and clinical trials introducing innovative radioimmunotherapy models. So far, the association of radiation with CSFs has not been combined with immunotherapy. However, it might play a major role in triggering an immune response against cancer cells, leading to abscopal effects. The present article reassesses the therapeutic index of the combination CSFs-chemoradiation through an updated review on its safety and efficacy. It also provides a special focus on radioimmunotherapy.
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http://dx.doi.org/10.1259/bjr.20190147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217575PMC
May 2020

[Docetaxel for octogerian metastatic castration-resistant prostate cancer patient: A multicentric ten years' experience].

Bull Cancer 2020 Feb 31;107(2):171-180. Epub 2019 Dec 31.

Institut de cancérologie Lucien-Neuwirth, département d'oncologie médicale, 108, bis avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France.

Introduction: There is very few data about the management of elderly patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze the management of patients aged 80 and over treated with docetaxel for a mCRPC.

Methods And Materials: Clinical and pathological characteristics of octogerians treated with docetaxel were collected retrospectively from 3 French centers from 2009 to 2019. Patient's outcome, treatments administered before and/or after docetaxel were also analyzed.

Results: Data of 89 patients could be analyzed. A total of 20.2 % of patients received the standard regimen and 79.8 % received an adapted one. Patients in the adapted group were significantly older than in standard one. Other patient's characteristics - including the geriatric scales - were similar. Dose reductions for toxicity were more frequent in the standard group (P=0.04). The median overall survival of the total population was 13.3 months. It was longer in the standard group than in the adapted group (26.1 months vs 12.4 months=0.01). In multivariate analysis, the type of docetaxel regimen (standard versus adapted) was an independent predictor of survival.

Conclusion: This study suggests the benefit of the standard management even in oldest patients. A geriatric evaluation should certainly be processed in patients with poor oncogeriatric scale in order to select the sub-population able to receive the full dose standard docetaxel regimen.
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http://dx.doi.org/10.1016/j.bulcan.2019.11.006DOI Listing
February 2020

[Radiotherapy and immune suppression: A short review].

Bull Cancer 2020 Jan 19;107(1):84-101. Epub 2019 Dec 19.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France; Institut de cancérologie Lucien-Neuwirth, département universitaire de recherche et éducation, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France.

The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.
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http://dx.doi.org/10.1016/j.bulcan.2019.09.010DOI Listing
January 2020

[Stereotactic body radiotherapy: Passing fad or revolution?]

Bull Cancer 2020 Feb 19;107(2):244-253. Epub 2019 Dec 19.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108, bis avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France; Institut de cancérologie Lucien-Neuwirth, département universitaire de la recherche et de l'enseignement, 108, bis avenue Albert-Raimond, BP60008, 42271 Saint Priest en Jarez cedex, France. Electronic address:

Stereotactic body radiotherapy (SBRT) is a young technology that can deliver a high dose of radiation to the target, utilizing either a single dose or a small number of fractions with a high degree of precision within the body. Various technical solutions co-exist nowadays, with particular features, possibilities and limitations. Health care authorities have currently validated SBRT in a very limited number of locations, but many indications are still under investigation. It is therefore challenging to accurately appreciate the SBRT therapeutic index, its place and its role within the anticancer therapeutic arsenal. The aim of the present review is to provide SBRT definitions, current indications, and summarize the future ways of research. There are three validated indications for SBRT: un-resecable T1-T2 non small cell lung cancer, <3 slow-growing pulmonary metastases secondary to a stabilized primary, and the tumours located close to the medulla. In other situations, the benefit of SBRT is still to be demonstrated. One of the most promising way of research is the ablative treatment of oligo metastatic cancers, with recent studies suggesting a survival benefit. Furthermore, the most recent data suggest that SBRT is safe. Finally, the SBRT combined with immune therapies is promising, since it could theoretically trigger the adaptative anticancer response.
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http://dx.doi.org/10.1016/j.bulcan.2019.09.011DOI Listing
February 2020

Use of Complementary and Alternative Medicines among Cancer Patients: A Single-Center Study.

Oncology 2019 27;97(1):18-25. Epub 2019 May 27.

Department of Supportive Care in Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France,

Purpose: It is usual for cancer patients to use complementary and alternative medicines (CAMs) and yet the literature evaluating their efficacy in cancer patients is very limited. The objective of the present study was to report on the nature, frequency of use, and patient-reported outcome of CAMs in a single-center study.

Methods: All the consecutive patients treated between November 2017 and June 2018 at the Lucien Neuwirth Cancer Institute (France) were screened. Their reasons for using CAMs and their usage habits were collected. Patients evaluated their benefit.

Results: Of the 209 patients screened, 200 patients were included. CAMs ranged from osteopathy, homeopathy, acupuncture, healing touch, magnetism, naturopathy, suction cups, Chinese medicine, reflexology, to hypnosis. CAMs were widely used (n = 166, 83%), the first being osteopathy (n = 99, 49.5%), the second homeopathy (n = 78, 39.0%), and finally acupuncture (n = 76, 38.0%). Whatever the CAM, high satisfaction rates were reported (median satisfaction: 61-81%). CAMs were mainly used to prevent/treat side effects of anticancer treatments (81.2% for healing touch), increase well-being (55.4% for naturopathy), improve the immune system (16.9% for homeopathy), and treat cancer (n = 3, 5.1% for homeopathy). Patients could easily consider using CAMs, as up to 50.8% would have accepted a consultation.

Conclusions: The reasons for using CAMs differed among patients. They praised CAMs and kept asking for more information although there is limited evidence about their efficacy in the literature. Thus, prospective randomized controlled trials exploring the safety and efficacy of CAMs in cancer patients are needed.
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http://dx.doi.org/10.1159/000499629DOI Listing
July 2019

BAM conditioning before autologous transplantation for lymphoma: a study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

Ann Hematol 2019 Aug 20;98(8):1973-1980. Epub 2019 May 20.

Centre Hospitalo-Universitaire Tours, Tours, France.

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.
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http://dx.doi.org/10.1007/s00277-019-03704-zDOI Listing
August 2019

[Complementary and alternative medicines in cancer patients].

Bull Cancer 2019 May 23;106(5):479-491. Epub 2019 Apr 23.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France.

Complementary and alternative medicines (CAMs) play more and more a significant role both in France and all over the world. Yet, their definition and their role in cancer treatments legitimately raise concerns. This article aims at establishing a picture of the CAMs admitted by the French Medical Board as well as those which are new or in common medical practices in France. We start with a brief reminder of their origin, their status and how they are used. Then, we review the literature about some of the best clinical trials using CAMs in cancer patients. To finish, we try to understand what makes CAMs so thrilling, but also why they create controversy and which common points they may have with conventional medicine.
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http://dx.doi.org/10.1016/j.bulcan.2019.02.011DOI Listing
May 2019

[LHRH analogs in adjuvant endocrine therapy for pre-menopausal localized breast cancers: Ending the controversy for novel guidelines?]

Bull Cancer 2019 Apr 8;106(4):342-353. Epub 2019 Mar 8.

Institut de cancérologie Lucien-Neuwirth, département de la recherche et de l'enseignement (DURE), 108 bis, avenue Albert-Raimond, 42271 Saint-Priest-en-Jarez, France; Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, 42271 Saint-Priest-en-Jarez, France. Electronic address:

Endocrine treatment represents the cornerstone of endocrine-sensitive pre-menopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management with surgery, radiotherapy and selective antiestrogen treatment. For several years, selective estrogen receptor modulators, such as tamoxifen, have revolutionized medical care of hormone receptors-positive breast cancer and have conquered the therapeutic arsenal while becoming the gold standard of treatment. Other combinations associating the ovarian function suppression using LHRH agonists with tamoxifen or aromatase inhibitors have been recently investigated, leading to mitigated opinions regarding the clinical benefit of these associations. We propose here a comprehensive overview on existing data and their actualization concerning LHRH analogues, whilst emphasizing benefit-risk balance for this targeted population.
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http://dx.doi.org/10.1016/j.bulcan.2019.01.012DOI Listing
April 2019

Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC).

Bone Marrow Transplant 2019 10 15;54(10):1586-1594. Epub 2019 Feb 15.

Institut de Cancérologie Lucien Neuwirth, Saint-Etienne, France.

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.
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http://dx.doi.org/10.1038/s41409-019-0475-7DOI Listing
October 2019

A complex mutational profile and a distinct clonal evolution during NPM1 myeloid sarcoma.

Leuk Lymphoma 2019 09 1;60(9):2328-2330. Epub 2019 Feb 1.

Laboratory of Hematology - Molecular Biology, University Hospital of Saint-Etienne , Saint-Etienne , France.

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http://dx.doi.org/10.1080/10428194.2019.1571199DOI Listing
September 2019

[Innovation in radiotherapy: A glance at 2018].

Bull Cancer 2019 Jan 4;106(1):48-54. Epub 2019 Jan 4.

Institut de cancérologie Lucien Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France; Département universitaire de la recherche et de l'enseignement, institut de cancérologie Lucien Neuwirth, 108, bis avenue Albert Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France.

Innovation in radiotherapy should meet multiple challenges, both technically, biologically, clinically and socially. Scientific, technological and biological advances have resulted in major changes in the implementation, indications, and therapeutic index of radiotherapy over the last century. Based on technical innovations (conformal radiotherapy, intensity modulation, CBCT, stereotactic body radiotherapy and MRI embedded system) and knowledge in cancer biology ("oxygen effect", "checkpoints", targeted therapies, molecular profiles and immunotherapy) highlighted in recent decades, the news in radiotherapy is rich and varied. The 2018 news are particularly focused in the role of hypofractionation in prostate cancer, the use of stereotactic body radiotherapy in oligometastatic patients, the possibility of de-intensify treatment in HPV-related oropharynx cancer, and the combination of short-term androgen deprivation to prostate bed salvage radiotherapy. The present manuscript reviews the 2018 latest advances.
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http://dx.doi.org/10.1016/j.bulcan.2018.12.006DOI Listing
January 2019

Fulminant hepatitis due to very severe sinusoidal obstruction syndrome (SOS/VOD) after autologous peripheral stem cell transplantation: a case report.

BMC Res Notes 2018 Jul 3;11(1):436. Epub 2018 Jul 3.

Department of Clinical Hematology, Institut de Cancérologie Lucien Neuwirth, 108 Bis Avenue Albert Raimond, 42270, Saint Priest en Jarez, France.

Background: Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (SOS/VOD), is a potentially fatal complication of allogeneic or autologous hematopoietic stem cell transplantation. A plethora of transplant and patient-related risk factors predispose to SOS/VOD and should be taken into account for prognosis assessment as well as for adequate therapeutic intervention.

Case Presentation: We describe the case of a mantle cell lymphoma patient who developed a fulminant hepatitis following oxaliplatin-containing intensive chemotherapy and autologous transplantation. This clinical manifestation was secondary to a very severe SOS/VOD. The patient did not exhibit the usual risk factors and presented a non-classical form with major cytolysis, thus puzzling SOS/VOD diagnosis in this context.

Conclusion: SOS has been previously reported after oxaliplatin-based chemotherapy regimens for colorectal cancers, in particular in patients with colorectal liver metastases. We therefore suspected a potential relationship with oxaliplatin-based regimen as a driver of SOS/VOD in a non-susceptible lymphoma patient. With regards to this case, clinicians and especially intensivists should be aware of this atypical presentation.
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http://dx.doi.org/10.1186/s13104-018-3533-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029059PMC
July 2018

[Pre-mRNA splicing: when the spliceosome loses ground].

Med Sci (Paris) 2016 Dec 3;32(12):1103-1110. Epub 2017 Jan 3.

Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.

Pre-mRNA splicing is an obligatory step required to assemble the vast majority of mRNAs in eukaryotes. In humans, each gene gives rise to at least two transcripts, with an average 6-8 spliced transcripts per gene. Pre-mRNA splicing is not unequivocal. Variations may occur, such that splicing can become alternative, thereby participating in increasing protein variability and restricting the gap that exists between the relatively low number of genes - between 20,000 and 25,000 in humans - and the much higher number of distinct proteins - at least 100,000. In addition, although alternative pre-mRNA splicing often fulfils cell-specific needs, many aberrant splicing events can happen and lead to either hereditary or acquired diseases such as neurodegenerative diseases or cancers. In those cases, alternative splicing events may serve as disease-associated markers, or even as targets for corrective approaches. In this review, we will summarize the main aspects of regulated alternative splicing. We will present the spliceosome, a large ribonucleoprotein complex that orchestrates the splicing reactions and that was recently identified as a preferential target for mutations in several pathologies. We shall discuss some spliceosome-associated defects linked to either cis (i.e on the DNA) or trans (e.g. in proteins) alterations of splicing machinery, like those that have been reported in genetic or acquired diseases.
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http://dx.doi.org/10.1051/medsci/20163212014DOI Listing
December 2016

The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches.

EMBO Rep 2015 Dec 13;16(12):1640-55. Epub 2015 Nov 13.

Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu-Fabra, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

Removal of introns from pre-mRNA precursors (pre-mRNA splicing) is a necessary step for the expression of most genes in multicellular organisms, and alternative patterns of intron removal diversify and regulate the output of genomic information. Mutation or natural variation in pre-mRNA sequences, as well as in spliceosomal components and regulatory factors, has been implicated in the etiology and progression of numerous pathologies. These range from monogenic to multifactorial genetic diseases, including metabolic syndromes, muscular dystrophies, neurodegenerative and cardiovascular diseases, and cancer. Understanding the molecular mechanisms associated with splicing-related pathologies can provide key insights into the normal function and physiological context of the complex splicing machinery and establish sound basis for novel therapeutic approaches.
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http://dx.doi.org/10.15252/embr.201541116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693517PMC
December 2015

Overexpression of MLN51 triggers P-body disassembly and formation of a new type of RNA granules.

J Cell Sci 2014 Nov 9;127(Pt 21):4692-701. Epub 2014 Sep 9.

Université de Rennes 1, UMR CNRS 6290 IGDR, «Translation and Folding Team», Campus de Beaulieu, 35042 Rennes cedex, France

Metastatic lymph node 51 (MLN51, also known as CASC3) is a core component of the exon junction complex (EJC), which is loaded onto spliced mRNAs and plays an essential role in determining their fate. Unlike the three other EJC core components [eIF4AIII, Magoh and Y14 (also known as RBM8A)], MLN51 is mainly located in the cytoplasm, where it plays a key role in the assembly of stress granules. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in P-body count is also observed in human HER2-positive (HER2(+)) breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation might correlate with cancer progression.
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http://dx.doi.org/10.1242/jcs.154500DOI Listing
November 2014

EJC core component MLN51 interacts with eIF3 and activates translation.

Proc Natl Acad Sci U S A 2013 Apr 25;110(15):5903-8. Epub 2013 Mar 25.

Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8197, 75230 Paris Cedex 05, France.

The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.
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http://dx.doi.org/10.1073/pnas.1218732110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625350PMC
April 2013

Perispeckles are major assembly sites for the exon junction core complex.

Mol Biol Cell 2012 May 14;23(9):1765-82. Epub 2012 Mar 14.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7104, Centre National de la Recherche Scientifique/U964 Institut National de Santé et de Recherche Médicale/Université de Strasbourg, 67404 Illkirch, France.

The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, and eIF4A3 form a highly stable EJC core, but where this tetrameric complex is assembled in the cell remains unclear. Here we show that EJC factors are enriched in domains that we term perispeckles and are visible as doughnuts around nuclear speckles. Fluorescence resonance energy transfer analyses and EJC assembly mutants show that perispeckles do not store free subunits, but instead are enriched for assembled cores. At the ultrastructural level, perispeckles are distinct from interchromatin granule clusters that may function as storage sites for splicing factors and intermingle with perichromatin fibrils, where nascent RNAs and active RNA Pol II are present. These results support a model in which perispeckles are major assembly sites for the tetrameric EJC core. This subnuclear territory thus represents an intermediate region important for mRNA maturation, between transcription sites and splicing factor reservoirs and assembly sites.
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http://dx.doi.org/10.1091/mbc.E12-01-0040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338441PMC
May 2012