Publications by authors named "Mery Benoite"

60 Publications

Body surface area capping may not improve cytotoxic drugs tolerance.

Sci Rep 2021 Jan 28;11(1):2431. Epub 2021 Jan 28.

Pharmacy Department, Lucien Neuwirth Cancer Center, 42270, Saint-Priest en Jarez, France.

Capping body surface area (BSA) at 2 m is a routine clinical practice. It aims at reducing toxicities in over 2 m BSA patients. 455,502 computerized chemotherapy prescriptions made between 2011 and 2017 were taken from BPC software. Chemotherapy computerized order entry is created by a senior physician prescribers before patient consultation. Only prescriptions with dose calculation involving BSA were selected. 51,179 chemotherapy prescriptions were analyzed; corresponding to 7206 patients who received intravenous chemotherapy. The number of chemotherapy prescriptions in over 2 m BSA patients was nearly the same in the hematology as in the oncology departments. But, 79.1% of prescriptions were capped at 2 m in the oncology department contrary to 21.9% in the hematology department. Practices analysis showed more dose limitation in palliative situations in both departments. Unexpectedly, 6.53% of capped prescriptions were performed in patients with normal BMI. The patients who received capped doses of chemotherapy had neither fewer dose reductions due to toxicity nor deterioration of their general condition. Capping did not induce fewer dose reductions in patients with BSA greater than 2 m. Prospective studies in this population are needed to standardize chemotherapy administration in population with BSA > 2 m.
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http://dx.doi.org/10.1038/s41598-021-81792-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843991PMC
January 2021

Effectiveness of a nurse-led telephone follow-up in the therapeutic management of patients receiving oral antineoplastic agents: a randomized, multicenter controlled trial (ETICCO study).

Support Care Cancer 2021 Jan 7. Epub 2021 Jan 7.

Medical Oncology Department, Lucien Neuwirth Cancer Institute, 108 bis Avenue Albert Raimond, 42270, Saint Priest en Jarez, France.

Purpose: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life.

Methods: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018.

Results: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point.

Conclusions: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD.

Trial Registration: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.
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http://dx.doi.org/10.1007/s00520-020-05955-3DOI Listing
January 2021

Predictive resistance factors in lung cancer patients treated with Nivolumab. Retrospective study.

Bull Cancer 2020 Dec 24. Epub 2020 Dec 24.

Institut de cancérologie Lucien-Newirth, Department of Medical Oncology, 108, bis avenue Albert-Raimond, 42270 Saint-Priest-en-Jarez, France.

Objectives: Immunotherapy is the current treatment in non-small cell lung cancer (NSCLC). 20% of patients treated with immunotherapy have a prolonged response. What about the remaining 80%? How can we explain that some patients get no benefit from immunotherapy?

Materiel And Methods: We retrospectively analyzed predictive factors of primary or secondary resistance to immunotherapy in NSCLC patients from 2 French hospitals between 2015 and 2018. Moreover, we evaluated whether PD1 inhibitor had an impact on the antitumor effects of salvage chemotherapy administered after immunotherapy. We chose to focus on taxanes.

Results: Ninety-six patients were included in this cohort, 65(68%) patients were considered as having primary resistance and 31(32%) secondary resistance. Resistant populations did not differ. At immunotherapy initiation, median survival was 4.6 months for primary resistant patients (95%CI-4.6-6.8) and 15.6 months (95%CI-9.8-NA) for secondary resistant patients. The disease control rates with taxane were 15% in pre immunotherapy conditions vs 50% in post immunotherapy. Response rates improved regardless of the status of resistance.

Conclusion: This study enriches data about immunotherapy in real-life in NSCLC. Prognostic resistance factors still seem complicated to identify. The high rate of taxane responders in post immunotherapy in this retrospective cohort support the use of taxane in therapeutic escape.
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http://dx.doi.org/10.1016/j.bulcan.2020.10.010DOI Listing
December 2020

Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review.

Semin Oncol 2020 Apr - Jun;47(2-3):103-116. Epub 2020 May 26.

Department of Medical Oncology, CHRU Jean Minjoz, Besançon cedex, France; Université de Franche-Comté, Besançon cedex, France; INSERM, Besançon cedex France.

Background: Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce.

Methods: Clinical data were searched through PubMed database until April 2020 according to PRISMA criteria. Efficacy, safety and pharmacokinetic (PK) assessment of ST were reported.

Results: Among 270 references, 56 reports were evaluated in full text: 41 were included for efficacy and 42 for safety analysis (sunitinib n = 68, bevacizumab n = 6, everolimus n = 28, temsirolimus n = 17, sorafenib n = 55, axitinib n = 13, pazopanib n = 13, nivolumab n = 18, cabozantinib n = 0, lenvatinib n = 0, and ipilimumab n = 0). Twelve of the reports included PK assessment among dialyzed patients. Hemodialysis did not seem to modify the expected efficacy and safety of each compound among patients undergoing hemodialysis. PK assessments were not modified in comparison with a population not undergoing dialysis.

Conclusion: Targeted and Immune therapies seem to be effective and can be used among patients undergoing hemodialysis. Due to frailty and comorbidities associated to chronic hemodialysis enhanced vigilance for these therapies within this specific population is recommended. Dedicated prospective clinical trials would definitely help to obtain data with a higher level of evidence.
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http://dx.doi.org/10.1053/j.seminoncol.2020.05.001DOI Listing
January 2021

Cardiovascular disease events within 5 years after a diagnosis of breast cancer.

BMC Cancer 2020 Apr 21;20(1):337. Epub 2020 Apr 21.

Department of Vascular and Therapeutic Medicine, University Hospital of Saint-Etienne, Saint-Etienne, France.

Background: Concern for cardiovascular disease (particularly atrial fibrillation-AF) among women with breast cancer is becoming a major issue. We aimed at determining the incidence of cardiovascular disease events (AF, arterial and cardiac events, venous-thromboembolism-VTE) in patients diagnosed with breast cancer, and assessing potential risk factors.

Methods: We reviewed medical records of all patients diagnosed with breast cancer from 2010 to 2011 in our cancer center. Baseline characteristics of patients and tumors were collected. The main outcome was the occurrence of cardiovascular disease events (AF, VTE, arterial and cardiac events) during the 5-years follow-up.

Results: Among the 682 breast cancer patients, 22 (3.2%) patients had a history of atrial fibrillation. Thirty-four patients (5%) presented at least one cardiovascular disease event, leading to a cumulative incidence of 5.8% events at 5-years ([3.8-7.7] CI 95%), with most of them occurring in the first 2 years. AF cumulative incidence was 1.1% ([0.1-2.1] CI 95%). Factors associated with the occurrence of cardiovascular disease events (including AF) were an overexpression of HER-2 (HR 2.6 [1.21-5.56] p < 0.011), UICC-stage III tumors or more (HR 5.47 [2.78-10.76] p < 0.001) and pre-existing cardiovascular risk factors (HR 2.91 [1.36-6.23] p < 0.004).

Conclusion: The incidence of cardiovascular disease events was 5.8% ([3.8-7.7] CI 95%), with HER-2 over-expression, UICC-stage III tumors or more and pre-existing cardiovascular diseases being associated with them. These findings call for the development of preventive strategies in patients diagnosed with breast cancer.
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http://dx.doi.org/10.1186/s12885-020-06838-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216603PMC
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

[From bench to bedside for new treatment paradigms in chordomas: An update].

Bull Cancer 2020 Jan 24;107(1):129-135. Epub 2019 Dec 24.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108, bis avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France. Electronic address:

Chordomas are rare malignant tumours, which typically occur in the axial skeleton and skull base. They arise from embryonic remnants of the notochord. They constitute less than 5 % of primary bone tumours. They are characterised by their locally aggressive potential with high frequency of recurrences and a median overall survival of 6 years. The initial therapeutic strategy must be discussed in an expert centre and may involve surgery, preoperative radiotherapy, exclusive radiotherapy or therapeutic abstention. Despite this, more than 50 % of patients will be facing recurrences with few therapeutic options available at this advanced stage. This review aims to outline current treatment options available in chordomas, as well as discussing potentiality of new therapeutic approaches through their molecular characterization and the comprehension of their immunological environment.
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http://dx.doi.org/10.1016/j.bulcan.2019.10.008DOI Listing
January 2020

[Posterior Reversible Encephalopathy Syndrome (PRES): About 4 cases].

Presse Med 2019 Oct 22;48(10):1026-1031. Epub 2019 Oct 22.

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

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http://dx.doi.org/10.1016/j.lpm.2019.08.019DOI Listing
October 2019

Current management of stage I testicular germ cell tumors in a French cancer institute. A practice analysis over the 10 past years.

Bull Cancer 2019 Dec 30;106(12):1086-1093. Epub 2019 Sep 30.

Institut de cancérologie Lucien-Newirth, Department of Medical Oncology, Saint-Priest-en-Jarez, France.

Background: Testicular Germ Cell Tumors (TGCTs) represent the most frequent malignant tumour among young male adults. Orchiectomy alone cure 80% of stage I. Standard options after orchiectomy include radiotherapy (RT), chemotherapy (CT) by 1 cycle of carboplatin AUC 7 or active surveillance (SV) for seminomatous GCTs (SGCT) and retroperitoneal lymphadenectomy (RPLND), CT by 1 or 2 cycles of Bleomycine Etoposide Cisplatine (BEP) or active surveillance for nonseminomatous GCTs (NSGCT). Adjuvant treatments decrease the relapse rate after orchiectomy with substantial toxicities without any benefit on overall survival. Recent guidelines accorded utmost importance on SV rather than adjuvants strategies. The main objective of this study was to describe our current practice over the 10 past years in regard of these recommendations.

Methods: Data of 50 patients with stage I GCT treated in our institute were collected between 2006 and 2016. Demographic and anatomopathologic data were reported. Clinical practice in our center was analyzed during two periods [2006-2011] and [2012-2016] according to the European Association of Urology Guidelines in 2011.

Results: Patient's median age was 35.3 years. The analysis of clinical practice during the last 10 years showed that in SGCT, main treatment was RT than SV and CT. This option declined over the years (89% between 2006-2010 versus 53% between 2011-2016) whereas SV was more often employed (27% between 2011-2016 versus none between 2006-2010). Surveillance was used for 64% of NSGCT.

Conclusions: In our center, RT was less used over the years for the benefit of SV which is recommended by guidelines.
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http://dx.doi.org/10.1016/j.bulcan.2019.08.012DOI Listing
December 2019

Maintenance Therapy in Metastatic Solid Tumors: Innovative Strategy or Simple Second-line Treatment?

Am J Clin Oncol 2019 08;42(8):615-623

Departments of Medical Oncology.

Managing metastatic diseases involves defining the best strategy that is supposed to take into account both efficacy and quality of life. To this end, clinicians use stop and go or maintenance strategies. As a matter of fact, 2 maintenance strategies can be distinguished: continuation maintenance using a drug already present in induction treatment and switch maintenance with a newly introduced drug. Several drugs have been approved as maintenance therapy with several current indications in solid tumors. Questions remain concerning such strategies, notably duration, cost, tolerability, and shortcut between switch maintenance and early second line. If the concept of maintenance strategy remains trendy with numerous trials ongoing, several issues are still pending. The aims of this review were to accurately define and describe the various facets of maintenance therapy through its several indications in real life and then to discuss the future challenges of maintenance therapy in oncology.
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http://dx.doi.org/10.1097/COC.0000000000000574DOI Listing
August 2019

[HPV: Carcinogenic implications and preventive measures].

Presse Med 2019 Jul - Aug;48(7-8 Pt 1):756-766. Epub 2019 Jul 12.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France; Laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud, CNRS UMR 5822, 165, chemin du grand Revoyet, BP 12, 69921 Oullins cedex, France. Electronic address:

Human oncogenic papillomaviruses (HPV) have an increasingly prominent role in the genesis of many cancers. The oncogenic mechanisms associated with HPV are now better known and make it possible to explain the etiopathogenesis of the association. HPV status is now sought for certain cancers and conditions both prognosis and management of patients. Preventive antiviral vaccination has become a real public health issue and aims to effectively reduce the prevalence of cervical, anal and oropharynx cancer, HPV-associated. However, vaccination against HPV still lags behind. The purpose of this review is to redefine the involvement of HPV in several cancers as well as current therapeutic challenges of HPV-related cancers, notably in term of prevention.
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http://dx.doi.org/10.1016/j.lpm.2019.05.019DOI Listing
September 2019

Efficacy and tolerance of thoracic radiotherapy in the oldest old patients: A case series.

Indian J Cancer 2019 Apr-Jun;56(2):163-166

Department of Medical Oncology and Radiotherapy, Institut de Cancérologie Lucien Neuwirth, 42271 Saint Priest en Jarez, France.

Background: There are only scarce data on the management of nonagenarians with lung cancer, and more particularly on the place of radiation therapy. The aim of the present study was to retrospectively evaluate the efficacy and tolerance of radiotherapy (RT) in nonagenarians with thoracic cancer.

Patients And Methods: Records from RT departments from four institutions were reviewed to identify patients 90 years old of age and older undergoing RT over the past decade for thoracic cancer and more particularly lung cancer. Tumors' characteristics as well as treatment specificities and its intent were examined.

Results: Thirteen patients receiving RT courses were identified, mean age 91.9 years. Treatment was given with curative and palliative intent in 15.4% and 84.6%, respectively. The median total prescribed dose was 30 Gy (4-70). The median number of fractions was equal to 10 (1-35). The median dose received for each fraction was 3 Gy (1.7-7). RT could not be completed in 2 patients (15.4%). At last follow-up, 11 patients (76.9%) were deceased, cancer being the cause of death for 90% of them. Most toxicities were grade 1 or 2. Two patients (15.4% of cases) have developed grade 2 toxicity during treatment. One patient (7.7% of cases) experienced an acute grade 3 toxicity.

Conclusion: The study shows that RT for thoracic cancer is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a certain measure of control with acceptable side effects.
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http://dx.doi.org/10.4103/ijc.IJC_346_18DOI Listing
September 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

High-throughput sequencing in clinical oncology: from past to present.

Swiss Med Wkly 2019 Mar 4;149:w20057. Epub 2019 Apr 4.

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

The war on cancer remains a major challenge as one of the hurdles for additional progress is the complexity of the mechanisms underlying the disease. Cutting-edge technologies and computing tools have led to whole genome sequencing as well as an integrated and inclusive omic approach of cancers with accurate molecular tumors' signatures through impressive progress in the field of Next Generation Sequencing (NGS). Genomic data may foster strategies for new drug development in addition to a better understanding of cancer genesis, opening a new era in oncology clinical practice. This review discusses the development of genomics approaches in cancer research and its perspectives for precision medicine, as well as clinical implications and remaining challenges.
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http://dx.doi.org/10.4414/smw.2019.20057DOI Listing
March 2019

Advocacy for a New Oncology Research Paradigm: The Model of Bevacizumab in Triple-Negative Breast Cancer in a French Cohort Study.

Oncology 2019 2;97(1):1-6. Epub 2019 Apr 2.

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

Background: Triple-negative breast cancer remains a disease with poor prognosis and few treatment options, due to the lack of therapeutic targets. Bevacizumab, the first anti-VEGF agent approved in the treatment of cancer, has demonstrated efficacy in breast cancer in combination with paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer. Despite the fact that the benefit was particularly significant for triple-negative breast cancer with its approval in 2008 by the FDA, this decision was later reversed as there was no improvement in overall survival in addition to significant costs.

Objectives: The scope of the present study is to focus on the role of bevacizumab in triple-negative breast cancer through the analysis of overall survival, progression-free survival, and cost benefit among 45 patients in a French monocentric study and to discuss new paradigms of endpoints.

Methods: All patients diagnosed with metastatic triple-negative breast cancer, for whom first-line treatment was bevacizumab in combination with paclitaxel between January 2011 and April 2018 were included in this single-center retrospective study, and a chart review of all recruited subjects was performed from medical records.

Results: In this real-life study among 45 patients with metastatic triple-negative breast cancer, bevacizumab provided a significant benefit for a category of patients, with longer median progression-free survival and the ability of maintenance therapy associated to limited side effects.

Conclusions: Beyond being the phoenix of breast oncology and a magnet of controversy, the case of bevacizumab in metastatic breast cancer highlights one of the greatest challenges in oncology, namely to balance modest clinical benefits with exponential costs. A balance needs to be found between health care affordability, high price of progress, and the best medical decision for the patients, in order to avoid the "unbreathable tipping point" we are actually dealing with.
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http://dx.doi.org/10.1159/000499583DOI Listing
July 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

Cancer du rein et radiothérapie : radiorésistance et au-delà.

Bull Cancer 2018 Dec;105 Suppl 3:S280-S285

Département de radiothérapie, institut de cancérologie Lucien-Neuwirth, 108 bis, avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez Cedex, France; Laboratoire de radiobiologie cellulaire et moléculaire, CNRS UMR 5822, Institut de physique nucléaire de Lyon, IPNL, 69622 Villeurbanne, France. Electronic address:

Kidney Cancer And Radiotherapy: RADIORESISTANCE AND BEYOND: Metastatic renal cancer has a poor prognosis because of the limited impact of usual treatment modalities, and notably radiotherapy. Renal cell carcinoma is traditionally considered to be radioresistant, and conventional radiotherapy fraction sizes of 1.8 to 2 Gy are thought to have little role in its management. Technological advances in radiation oncology have led to stereotactic approaches that overcome radio resistance mechanisms of renal cancer cells and could be successful. The technical ability of applying high dose per fraction, leads to a distinct biological response which is different from the one observed with conventional irradiation through high responses rates. The increased radiobiological effect is attributed to endothelial apoptosis triggered by high fractional dose. The combination of such radiotherapy regimens with targeted drugs paves the way for new therapeutic opportunities.
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http://dx.doi.org/10.1016/S0007-4551(18)30383-7DOI Listing
December 2018

Cancer du rein métastatique : recommandations et perspectives en 1 ligne.

Bull Cancer 2018 Dec;105 Suppl 3:S235-S241

Département de radiothérapie, Institut de Cancérologie Lucien Neuwirth, Saint Priest en Jarez, France. Electronic address:

Metastatic Renal Cell Carcinoma: WHICH TREATMENTS IN FIRST-LINE SETTING?: The treatment of metastatic kidney cancer has radically changed during the past decade, notably with the development of tyrosin kinase inhibitors (TKI) and the rise of immunotherapy. Kidney cancer, especially clear cell renal cell carcinoma (CCRC) which regroups 80% of cases, is associated with increased angiogenesis and VEGF (vascular endothelial growth factor) dependent signaling pathways. Targeted therapies have therefore modified therapeutical strategies through direct inhibition of VEGF on its receptor or inhibition of the PI3K/AKT/mTOR pathway. Consequently, new anti-angiogenic molecules are now available as first line treatment and are to be prioritized depending on tumoral histology and prognostic groups. These new molecules have allowed increased patient survival. Immunotherapy is again currently transforming our first line therapeutical approach of metastatic kidney cancer with numerous ongoing therapeutical trials including combination of targeted therapies with immune checkpoint inhibitors or association of various immunotherapies. Beyond these major first line changes, difficulties still remain in the therapeutical sequence which is crucial in the care of these patients. This report aims to underline first line therapeutical recommendations in metastatic kidney cancer and expose results of recent assays.
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http://dx.doi.org/10.1016/S0007-4551(18)30378-3DOI Listing
December 2018

Cancer du rein : tendances et perspectives.

Bull Cancer 2018 Dec;105 Suppl 3:S219-S220

Département de radiothérapie, institut de cancérologie Lucien-Neuwirth 108 bis, avenue Albert-Raimond, BP 60008, 42270 Saint-Priest-en-Jarez, cedex, France. Electronic address:

New Trends And Perspectives In Renal Cell Cancer: Š.
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http://dx.doi.org/10.1016/S0007-4551(18)30375-8DOI Listing
December 2018

Biological aspects of chondrosarcoma: Leaps and hurdles.

Crit Rev Oncol Hematol 2018 Jun 22;126:32-36. Epub 2018 Mar 22.

Radiotherapy Department, Lucien Neuwirth Cancer Institute, St Priest en Jarez, France.

Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches.
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http://dx.doi.org/10.1016/j.critrevonc.2018.03.009DOI Listing
June 2018

Dual "mAb" HER family blockade in head and neck cancer human cell lines combined with photon therapy.

Sci Rep 2017 09 22;7(1):12207. Epub 2017 Sep 22.

Université Lyon 1, UMR CNRS 5822 /IN2P3, IPNL, PRISME, Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, F-69921, Oullins cedex, France.

Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation. Cell proliferation, migration and invasion were studied after treatment with cetuximab +/- pertuzumab +/- 10 Gy photon irradiation. EGFR, phospho-EGFR, HER2 and HER3 protein expression levels were studied. Activation or inhibition of the RAS/MAPK and AKT-mTOR downstream signalling cascades was investigated through phospho-AKT and phospho-MEK1/2 expression. Cetuximab strongly inhibited SQ20B and FaDu cell proliferation, migration and invasion, whereas it had little effect on SQ20B-CSCs. Cetuximab-pertuzumab combined with radiation significantly inhibited SQ20B and FaDu cell and SQ20B-CSC proliferation, migration and invasion. Cetuximab-pertuzumab with 10 Gy photon irradiation switched off both phospho-AKT and phospho-MEK1/2 expression in the three populations. The triple therapy is therefore thought to inhibit SQ20B cells, SQ20B-CSCs and FaDu cells through an AKT-mTOR and Ras-MAPK downstream signalling blockade.
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http://dx.doi.org/10.1038/s41598-017-12367-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610257PMC
September 2017

[Immunotherapy: Activation of a system not a pathway].

Bull Cancer 2017 May 3;104(5):462-475. Epub 2017 May 3.

Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez cedex, France; CNRS UMR 5822, laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud, 165, chemin du Grand-Revoyet, BP 12, 69921 Oullins cedex, France. Electronic address:

Immunotherapy is on the roll. After revolutionary effects in melanoma, immunotherapy is invading other locations. If current treatments, chemotherapies or targeted therapies block one pathway, immunotherapy should be understood as the activation of a whole system. Indeed, oncogenesis process is defined as an escape of the immune system and the stimulation of this system can block the carcinogenic process. The aim of the present review is to describe the place of immunotherapy in the treatment of solid cancers.
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http://dx.doi.org/10.1016/j.bulcan.2017.03.004DOI Listing
May 2017

In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues.

J Cell Death 2017 24;10:1179670717691251. Epub 2017 Feb 24.

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

Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.
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http://dx.doi.org/10.1177/1179670717691251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392044PMC
February 2017

Atrial fibrillation in cancer patients: Hindsight, insight and foresight.

Int J Cardiol 2017 Aug 6;240:196-202. Epub 2017 Apr 6.

Department of Vascular and Therapeutic Medicine, University Hospital of Saint-Etienne, France; INSERM, CIC1408, Saint-Etienne, France; INSERM, U1059, Vascular Dysfunction and Homeostasis, Saint-Etienne, France.

An increase of atrial fibrillation (AF) incidence in cancer patients has recently been pointed out, with complex interrelationships between these two entities on top of surgery factors. Most of present knowledge comes from retrospective studies or data from registries but the underlying mechanisms of the association between atrial fibrillation and cancer are still unclear. An increased risk of AF in cancer patients could represent a major public health problem although scarce information is available for the challenging management of such patients with distinctive features, especially in terms of antithrombotic therapy. Elaborate evidence-based approaches are thus required. This review provides an insight into AF among cancer patients through an overview of the underlying mechanisms, epidemiology evidence and future therapeutic challenges.
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http://dx.doi.org/10.1016/j.ijcard.2017.03.132DOI Listing
August 2017

Quality of reporting in oncology studies: A systematic analysis of literature reviews and prospects.

Crit Rev Oncol Hematol 2017 Apr 24;112:179-189. Epub 2017 Feb 24.

Hygee Center, Regional Center for Cancer Prevention, CIC 1408, Saint Priest en Jarez, France; EMR3738, Ciblage Thérapeutique en Oncologie, Claude Bernard University, Lyon, France; Jean Monnet University, Saint-Etienne, France.

The present review gives an overview of systematic reviews published in peer reviewed Journals analysing quality of reporting in oncology studies. PUBMED and Cochrane library were searched to identify systematic reviews assessing quality of reporting for randomized controlled trials (RCTs) and observational studies (OBS). Recommendations and primary endpoints used to assess the quality of reporting were described. Intrinsic quality of reporting was analyzed using an Overall Quality Score for literature Reviews (OQSR). Main evaluation themes were overall quality of reporting (20/58) and reporting of Health-Related Quality Of Life (HRQOL) in RCTs (7/58). Reporting recommendations used were not detailed in 56.9% of reviews. Insufficient reporting for the methodological description (randomization, blinding details, and allocation concealment) and the rationale for using specific measure of HRQOL were highlighted. OQSR was significantly higher for reviews published between 2010 and 2014 (after the PRISMA Publication), as compared to those published between 1996-2009 (median OQSR 10 (10-11) versus median OQSR 9 (6-10) respectively, p=0.0053). Intrinsic quality of reporting is satisfactory and has been improved in the last years.
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http://dx.doi.org/10.1016/j.critrevonc.2017.02.012DOI Listing
April 2017

Preclinical models in HNSCC: A comprehensive review.

Oral Oncol 2017 02 28;65:51-56. Epub 2016 Dec 28.

Université Lyon 1, Faculté de Médecine-Lyon-Sud, 69921 Oullins, France; Laboratoire de Radiobiologie Cellulaire et Moléculaire, CNRS UMR 5822, Institut de Physique Nucléaire de Lyon, IPNL, 69622 Villeurbanne, France; Département de Radiothérapie, Institut de Cancérologie de la Loire - Lucien Neuwirth, 42270 St Priest en Jarez, France. Electronic address:

Head and neck cancer remains a significant public health concern. About 60% of patients die within 5years due to local recurrence. Head and neck squamous cell carcinoma (HNSCC) cell lines are important preclinical models in the search for new therapies against this disease. Furthermore, there is a need to test novel drugs before introduction into clinical practice. A preclinical model that closely resembles the in vivo situation would be highly valuable. In the last few decades, a multicellular spheroid model has gained attention as its behavior was comparable to in vivo tumors. Basic research is necessary to achieve an understanding of the normal and pathological state but cannot, in itself, provide sufficient information for clinical applications. Indeed, animal models are an inevitable prelude to assess the efficacy of new therapeutic approaches in HNSCC. The present review proposes an overview of HNSCC pre-clinical models in order to further understand the oncogenic properties for HNSCC and translate these findings into clinic for patients.
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http://dx.doi.org/10.1016/j.oraloncology.2016.12.010DOI Listing
February 2017

[Reappraisal role of locoregional radiation therapy in metastatic cancers].

Bull Cancer 2017 Jan 9;104(1):86-91. Epub 2016 Dec 9.

Institut de cancérologie Lucien-Neuwirth, département universitaire de la recherche et de l'enseignement, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP 60008, 42271 Saint-Priest-en-Jarez, France; Laboratoire de radiobiologie cellulaire et moléculaire de Lyon Sud - CNRS UMR 5822, 165, chemin du Grand-Revoyet, BP 12, 69921 Oullins cedex, France. Electronic address:

Recent innovations in oncology area helped to improve the prognosis of certain cancers including metastatic ones with a decrease in mortality. Recommendations describe the treatment of metastatic cancer as systemic therapy or complementary care and the role of locoregional treatment in the treatment plan only occurs in a palliative context. Currently, in the clinical practice, out of "the evidence based medicine", an early locoregional therapy (surgery or radiation therapy) can be proposed in several cases of metastatic cancers. The aim of the present review is to describe the role of the primary tumor radiation therapy in metastatic disease. In metastatic breast, prostate, cervix, rectal or nasopharyngeal cancers, locoregional treatment including radiation therapy can, in some cases, be discussed and decided in MDT. Ongoing clinical trials in these locations should soon precise the benefit of this locoregional treatment. It will also be important to define the specific criteria in order to select patients who could benefit from this treatment.
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http://dx.doi.org/10.1016/j.bulcan.2016.11.008DOI Listing
January 2017

Les métastases des cancers.

Rev Prat 2016 Sep;66(7):e298

Département d'oncologie médicale, institut de cancérologie Lucien-Neuwirth, 42270 Saint-Priest-en-Jarez, France.

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September 2016

Signes d'appel et investigations paracliniques ; caractérisation du stade ; pronostic.

Rev Prat 2016 Sep;66(7):e291-e297

Département d'oncologie médicale, institut de cancérologie Lucien-Neuwirth, 42270 Saint-Priest-en-Jarez, France.

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September 2016