Publications by authors named "Alexis Vallard"

82 Publications

Persistent High-Risk HPV Infection and Molecular Changes Related to the Development of Cervical Cancer.

Case Rep Obstet Gynecol 2020 23;2020:6806857. Epub 2020 Jul 23.

Department of Radiation Oncology, Institut de cancérologie de la Loire-Lucien Neuwirth, 108 bis, Avenue Albert Raimond, BP 60008, 42271 Saint-Priest en Jarez, France.

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1R, IGF1R, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1R, IGF1R, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.
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http://dx.doi.org/10.1155/2020/6806857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845664PMC
July 2020

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

hTERT Protein Expression in Cytoplasm and Nucleus and its Association With HPV Infection in Patients With Cervical Cancer.

Cancer Genomics Proteomics 2020 Sep-Oct;17(5):615-625

Department of Radiation Oncology, Institut de Cancérologie de la Loire-Lucien Neuwirth, Saint-Priest en Jarez, France.

Background: Few studies have analyzed the association between human telomerase reverse transcriptase (hTERT) protein expression (nuclear and cytoplasmic localization), hTERT methylation status, and human papillomavirus (HPV) genotype infection in cervical cancer.

Patients And Methods: One hundred seventy-three patients with cervical cancer were analyzed. hTERT protein expression was detected by immunohistochemistry. hTERT DNA methylation analysis was performed using a PCR-RLB-hTERT assay, targeting two regions of the hTERT promoter. Type specific HPV infection was detected by using GP5+/GP6+PCR-RLB.

Results: hTERT protein expression was found in both cytoplasm and nucleus (78.0% of the samples showed a cytoplasmic localization and 79.8% had a nuclear localization). A statistically significant association was found between alpha 9 and 7 HPV species with a non-methylation pattern of the hTERT promoter and between these species and high expression of hTERT protein with nuclear localization.

Conclusion: hTERT protein is found in both the nucleus and cytoplasm of patients with cervical cancer and confirm the relationship between the non-methylated status of hTERT promoter and some HPV species as well as the relationship between these species and hTERT protein expression.
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http://dx.doi.org/10.21873/cgp.20218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472445PMC
March 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

Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

Radiat Oncol 2020 Jun 8;15(1):145. Epub 2020 Jun 8.

SAINBIOSE U1059, Jean Monnet University, Saint-Etienne, France.

Background: Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line.

Materials/methods: We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors.

Results: 2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose.

Conclusions: Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.
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http://dx.doi.org/10.1186/s13014-020-01584-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278121PMC
June 2020

CBCT evaluation of inter- and intra-fraction motions during prostate stereotactic body radiotherapy: a technical note.

Radiat Oncol 2020 Apr 19;15(1):85. Epub 2020 Apr 19.

Department of radiation oncology, Lucien Neuwirth Cancer Institute, 108 Bis, Avenue Albert Raimond, 42270, Saint Priest en Jarez, France.

Background: In most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT).

Methods: Data about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs.

Results: Eight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29 cc) but significant (p < 0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4 cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement.

Conclusion: Major prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc.

Trial Registration: NCT02361515, February 11th, 2015.
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http://dx.doi.org/10.1186/s13014-020-01534-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168857PMC
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

[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

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

[Will France ever have a radio-vigilance office?]

Bull Cancer 2019 Dec 23;106(12):1067-1069. Epub 2019 Jul 23.

Hôpital S. Maria alle Scotte, université de Sienne, département de science médicale, chirurgicale et neurologique, unité de dermatologie, Sienne, Italie.

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http://dx.doi.org/10.1016/j.bulcan.2019.05.007DOI Listing
December 2019

Special Focus on Stage IV Cervical Cancer Patients: A Decade Experience.

Oncology 2019 2;97(3):125-134. Epub 2019 Jul 2.

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

Objectives: The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stage IVA) and metastatic CC (i.e., stage IVB).

Method: A retrospective review was conducted based on all consecutive patients treatedfor stage IV CC in a comprehensive cancer care centre between 2004 and 2017.

Results: Sixty-eight patients were included. Performance status (PS) was ≥2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph node metastases (38.6%), 13 had only distant metastases (29.5%), and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n = 14, 58.3%) +/- concomitant chemotherapy, or a palliative treatment (n = 10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), 11 a primary concomitant chemoradiation (25%), and 10 a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stage IVA (95% CI = 0.7-33.9), and 10.5% for stage IVB (95% CI = 3.7-29.7). In multivariate analysis, PS >1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS >1 and pelvic lymph node involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC.

Conclusions: In daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies.
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http://dx.doi.org/10.1159/000500025DOI Listing
September 2019

Drug Management in End-of-Life Hospitalized Palliative Care Cancer Patients: The RHESO Cohort Study.

Oncology 2019 20;97(4):217-227. Epub 2019 Jun 20.

Centre Hygée, Public Health Department, Lucien Neuwirth Cancer Institute, Saint-Priest en Jarez, France.

Objective: Little data about the management of drugs in terminally ill palliative care cancer patients is available. The present study aimed at describing the evolution of anticancer and non-anticancer treatments (NACTs) in cancer patients in palliative care units. The second objective was to identify factors leading to the medical decision to withdraw or not NACTs.

Methods: Data from 1,091 cancer patients hospitalized in palliative care units were prospectively collected in 2010-2011, through a multicenter, observational French cohort.

Results: The median overall survival after admittance in palliative care units was 15 days. Specific anticancer treatments were systematically stopped in the first 24 h in palliative care units, but for 4.5% of patients. Regarding NACTs, patients were heavily treated with strong opioids (74%), corticosteroids (51%), and antidepressants (21.8%) until death. Antiulcer agents (63.4%), antibiotics (25.7%), thrombosis prevention (21.8%), antidiabetics (7.6%), and transfusions (4%) were often also continuously prescribed. In multivariate analysis, ECOG PS 4 was an independent predictor of continuous prescription of morphine and an independent predictor of discontinuation of corticosteroids, proton-pump inhibitors, antidiabetics, and preventive anticoagulant therapy. Infection symptoms independently predicted continuous prescription of paracetamol. Paralysis and cancer palpable mass independently predicted corticosteroid withdrawal. Brain metastases independently predicted antiulcer withdrawal. Hemorrhage independently predicted preventive anticoagulant withdrawal. Availability to a venous access independently predicted paracetamol and antiulcer continuous prescriptions. Co-prescriptions independently predicted continuous prescriptions (antibiotics with antiulcer, antifungals with antibiotics) or withdrawal (preventive anticoagulant with antiplatelets and antifungals).

Conclusions: NACT prescription remained commonplace in terminally ill palliative cancer patients, although their benefit is questionable.
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http://dx.doi.org/10.1159/000500783DOI Listing
October 2019

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

[Brachytherapy: When needs overtake care offer].

Bull Cancer 2019 Jun 10;106(6):584-589. Epub 2019 May 10.

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

Brachytherapy has the unique characteristic of being able to deliver high doses to a very localized volume, and remains one of the radiotherapy techniques that has an unparalleled therapeutic index. However, its use has been declining in the past years. Globally, only 55 to 88 % of patients with locally advanced cervical cancer benefit from utero-vaginal brachytherapy, despite the fact that it is proven to enhance both progression-free and overall survival. A decline in the use of low dose rate brachytherapy has likewise been described in the treatment of low-risk and favorable intermediate-risk prostate cancers. Several factors could explain this. First, the radiation oncologists who have the proficiency to perform brachytherapy seems to be inadequate, as it is a technique that requires training and expertise for optimal applications. In many cancer care centers, the caseload is insufficient to provide this experience. Second, the increasing use of technically advanced external beam radiation therapy, such as intensity modulated radiation therapy, offers an easier substitute with more lucrative benefits, resulting in decreased utilization of brachytherapy. However, when brachytherapy is not delivered, a poorer survival rate is reported in locally advanced cervical cancer, and is suggested in intermediate and high-risk prostate cancer. The increasing level of evidence of treatment with brachytherapy necessitates an improvement in its accessibility by having more radiation oncologists as well as cancer centers equipped to perform the procedure.
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http://dx.doi.org/10.1016/j.bulcan.2019.03.017DOI Listing
June 2019

Chemoradiation phase II trials: re-exploring a world of missed opportunities.

Acta Oncol 2019 Aug 10;58(8):1158-1162. Epub 2019 May 10.

a Department of Radiation Oncology , Lucien Neuwirth Cancer Institute , Saint-Priest-en-Jarez , France.

Phase II trials are designed to assess the efficacy/toxicity ratio of experimental treatments and select those worth being tested in phase III trials. Although crucial limitations were identified when concurrent chemoradiation (cCRT) phase III trials characteristics were assessed, features of cCRT phase II trials have never been reported. The objective was to describe features of all cCRT phase II trials. Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase II as topic', 'chemoradiotherapy'. Four hundred and fifty-eight cCRT phase II trials were identified. They were mainly multicenter (51.5%), single arm studies (77.7%) published after 2011 (55.0%). The median number of included patients was 52. Primary endpoints were mainly response rate (20.5%), pathological complete response (14.4%) and overall survival (12.6%). The primary endpoint was not defined in 22% of studies. Tumors were mostly lung (23.1%), head and neck (20.3%), colorectal (16.6%) and esophagogastric cancer (14.6%) treated at a locally advanced setting (81.7%). 55.2% of trials used 3D-conformal radiotherapy and 9.1% intensity-modulated radiotherapy, mainly with normo-fractionation (82.0% of the 573 arms with radiotherapy). Radiation technique was not reported in 19.9% of studies. Associated anticancer drugs (563 arms) were mainly conventional chemotherapies (559 arms): cisplatin (46.2%) and 5-fluorouracil (28.3%). Non cytotoxic agents (targeted therapies, immunotherapies) were tested in 97 arms (17%). With a median follow-up of 31 months, acute grades 3-5 were reported in 98.5% of studies and late toxicities in 44.5%. Follow-up was not reported in 17% of studies. cCRT phase II trials featured severe limitations, with outdated radiation techniques, insufficient reporting of crucial data and a small number of included patients. This certainly limited the impact of conclusions and hindered the development of successful phase III trials.
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http://dx.doi.org/10.1080/0284186X.2019.1605194DOI Listing
August 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

Quality insurance in head and neck cancer multidisciplinary team meetings: A watchful eye on real-life experience.

Oral Oncol 2019 04 26;91:35-38. Epub 2019 Feb 26.

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

Introduction: Although Multidisciplinary Team Management (MDT) is integrated in most international head and neck cancer treatment guidelines, its applications and proceedings were rarely described. The present study explores a 6-year real-life experience in a French Comprehensive Cancer Care Center.

Methods: Patients, tumor and meeting characteristics of all consecutive cases discussed in head and neck MDT meetings between 2010 and 2015 were retrospectively reviewed.

Results: From 2010 to 2015, 1849 cases (accounting for 1786 patients) were discussed in 138 MDT meetings. Median age was 62 (range: 15-96). When reported (n = 310, 16.8%), performance status was ≥2 in 36.1% of patients. Tumors were mainly squamous cell carcinomas (n = 1664, 91.5%) of the larynx/hypo-pharynx (n = 630, 34.4%), oropharynx (n = 518; 28.3%) and oral cavity (n = 339; 18.5%). Tumors were diagnosed at a locally (n = 358, 25%), locally advanced (n = 946, 66%) or metastatic setting (n = 53, 3.7%). Mean number of discussed patients per MDT meeting was 16 (range: 3-32). Most patients were discussed once (n = 1663, 97%). Most patients (n = 969, 52%) underwent treatment before MDT meetings: mainly surgery (n = 709, 73.2%). The mean time between MDT meeting and first radiation course was 21 days (range: 1-116).

Discussion: Optimal multimodal treatment management is based on MDT meetings and results from the interaction and coordination of surgeons, medical and radiation oncologists. In the present series, most patients were discussed once despite the number of expected recurrences, suggesting that the management of tumor progression was not discussed in head and neck MDT meetings. Furthermore, most patients had surgery before MDT meeting, pointing out that MDT role and place still needs to be improved. Finally, the present population significantly differed from patients included in phase III clinical trials, with more advanced age and poorer condition. It calls for the necessity of a high-quality head and neck MDT meeting since evidence-based recommendations should be adapted to patient's frailties.
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http://dx.doi.org/10.1016/j.oraloncology.2019.02.020DOI Listing
April 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

Is breast-conserving therapy adequate in BRCA 1/2 mutation carriers? The radiation oncologist's point of view.

Br J Radiol 2019 May 27;92(1097):20170657. Epub 2019 Feb 27.

3 Department of Radiotherapy, Institut Gustave Roussy , Villejuif , France.

Breast conserving therapy (BCT) is currently a recognized alternative to mastectomy for early BC patients. However, the therapeutic index of BCT was considered controversial for decades in BRCA1/2 mutation carriers. The aim of the present review was to investigate the outcome of mutation carriers undergoing BCT regarding local and distant endpoints. A short review was performed from the point of view of the radiation oncologist. Only retrospective data were available regarding local outcome assessment. They generated conflicting results. In studies with limited follow-up, BCT did not increase the risk of local recurrence in BRCA1/2 mutation carriers non-carriers. Conversely, some studies with longer follow-up supported that local relapse was increased in mutation carriers. Yet, according to some publications, their long-term risk of ipsilateral recurrence post-BCT was not different from general population cohorts. Besides, overall and metastasis-free survivals were the same after BCT regardless of the BRCA1/2 mutation status. Similar survival rates were also reported when BCT and mastectomy were compared in mutation carriers. Regarding acute or late toxicity, normal rates were reported in BRCA mutation carriers after breast radiotherapy. The BRCA1/2 mutation does not seem to widely alter the therapeutic index (efficacy/toxicity ratio) of modern adjuvant breast irradiation. Although the long term equivalence of BCT/mastectomy on local control is still not clearly recognised, BCT can be considered an adequate option for BRCA1/2 mutation carriers. This review highlights that BCT is a reasonable option for BRCA1/2 mutation carriers however litterature is controversial concerning long-term local outcome and results of a large prospective cohort are needed.
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http://dx.doi.org/10.1259/bjr.20170657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580916PMC
May 2019

Safety assessment of anticancer drugs in association with radiotherapy in metastatic malignant melanoma: a real-life report : Radiation/systemic drug combo in metastatic melanoma.

Cancer Chemother Pharmacol 2019 05 26;83(5):881-892. Epub 2019 Feb 26.

Institut de Cancérologie Lucien Neuwirth, 108 bis Avenue Albert Raimond, BP 60008, 42271, St Priest en Jarez cedex, France.

Purpose: To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM).

Methods: A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatments were defined as sequential or concomitant when RT and the systemic drug were administered, respectively, at more or less than five half-lives from each other.

Results: 92 patients were included. They had 110 palliative RT treatments. RT was delivered with a "conventional" chemotherapy (mainly fotemustine and/or dacarbazine) and a "modern" systemic therapy (BRAF inhibitors, association of BRAF and MEK inhibitors, immunotherapy), respectively, in 88 (80%) and 22 (20%) cases. Systemic treatments and RT were mainly concurrently performed (n = 61, 55.5%). Regarding acute grade ≥ 3 toxicity, no difference was reported between sequential and concomitant groups either in the whole cohort (p = 1) or in the subgroup of patients receiving "modern" systemic therapies (p = 1). Acute and late grade ≥ 3 toxicities only occurred with vemurafenib. BRAF inhibitors and RT produced more severe infield adverse events than other associations (p = 0.001) with two deaths.

Conclusion: In our series, compared to sequential administration, concomitant association of systemic anticancer drugs and palliative RT did not increase toxicity in mMM patients. BRAF inhibitors and RT produced severe infield toxicities. Prospective studies are needed to better characterize the toxicity of each association.
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http://dx.doi.org/10.1007/s00280-019-03806-5DOI Listing
May 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

Radiothérapie et immunothérapie.

Bull Cancer 2018 Dec;105 Suppl 1:S92-S100

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:

Radiation Therapy And Immunotherapy: Nowadays, it is known and recognized that the immune system has a central place in the mechanisms of oncogenesis and the effectiveness of anti-cancer therapies. The demonstration of the immuno-stimulatory ability of radiation therapy opens the field to new applications for this therapy already widely used in oncology area. Indeed, radiotherapy is capable of initiating and / or increasing the immune-mediated anti-tumor response. The combination of this "old" therapy with the "new" therapies that are immunotherapies then makes perfect sense. Although the potentiating effect of this combination is based on an interesting and well-documented biological rationale in preclinical data, there are still few clinical data available. The multiplication of trials, and the arrival of phase III trials should give us more perspective on the effectiveness and safety of this association. However, the lack of consensus concerning the optimization of these "immuno-radiotherapies" (characteristics of the tumor, irradiation regimen and treatment plan) could prove deleterious for the results of ongoing studies.
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http://dx.doi.org/10.1016/S0007-4551(18)30394-1DOI Listing
December 2018

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