Publications by authors named "Nicolas Magné"

272 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

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

MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma.

Cancers (Basel) 2021 Jan 7;13(2). Epub 2021 Jan 7.

Radiation Oncology Department, Hôpital Haut-Lévêque, CHU Bordeaux, 33600 Pessac, France.

Purpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC).

Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis.

Results: A total of 82 patients were randomized in the training ( = 54) and testing sets ( = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, = 0.005).

Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine.
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http://dx.doi.org/10.3390/cancers13020193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827348PMC
January 2021

[What should we remember from 2020?]

Bull Cancer 2021 Jan 6;108(1):55-66. Epub 2021 Jan 6.

Université de Bordeaux, Inserm U1218, 33000 Bordeaux, France.

The editorial committee of the Bulletin du Cancer is proud to comply with his annual analysis of some of the worldwide updates in oncology that emerge in 2020. We know that all new breakthroughs will not be addressed and apologise for not being comprehensive, but we hope that the topics deciphered herein will bring the reader interesting information in his daily practice in gyneco-oncology, uro-oncology, neuro-oncology, digestive oncology, pneumo-oncology, hemato-oncology, pediatric oncology, or in palliative care.
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http://dx.doi.org/10.1016/j.bulcan.2020.12.002DOI Listing
January 2021

Vaccination and Immune Checkpoint Inhibitors: Does Vaccination Increase the Risk of Immune-related Adverse Events? A Systematic Review of Literature.

Am J Clin Oncol 2021 Mar;44(3):109-113

Medical Oncology Department.

Introduction: Immune checkpoint inhibitors (ICIs) have become part of cancer treatments. Their main side effects are immune-related adverse events (irAEs). So far, there has been no recommendation regarding routine vaccinations during ICIs treatment. Clinicians are aware of the risk of irAEs increases in this specific situation. The aim of this review of literature is to summarize the main studies about vaccination and ICIs interactions.

Methods: A systematic assessment of literature articles was performed by searching in PubMed (MEDLINE), and major oncology meeting following PRISMA guidelines.

Results: This review highlights the lack of literature. Indeed, most of the studies published were about influenza vaccination. Vaccination for patients under ICIs causes a humoral response and seems to be associated with an increase rate of seroconversion. Interestingly vaccination may provoke irAEs in ICIs-treated patients. So far, inactivated vaccines have not been contraindicated during ICI treatment.

Conclusion: Larger prospective studies are needed in order to define a consensus on the use of vaccines under immunotherapy.
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http://dx.doi.org/10.1097/COC.0000000000000788DOI Listing
March 2021

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

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

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

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

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

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

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

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

Positron emission tomography for radiotherapy planning in head and neck cancer: What impact?

Nucl Med Commun 2021 Mar;42(3):234-243

Service de Médecine Nucléaire, Centre Hospitalier Universitaire de Saint-Etienne, St Etienne.

PET-computed tomography (CT) plays a growing role to guide target volume delineation for head and neck cancer in radiation oncology. Pretherapeutic [18F]FDG PET-CT adds information to morphological imaging. First, as a whole-body imaging modality, it reveals regional or distant metastases that induce major therapeutic changes in more than 10% of the cases. Moreover, it allows better pathological lymph node selection which improves overall regional control and overall survival. Second, locally, it allows us to define the metabolic tumoral volume, which is a reliable prognostic feature for survival outcome. [18F]FDG PET-CT-based gross tumor volume (GTV) is on average significantly smaller than GTV based on CT. Nevertheless, the overlap is incomplete and more evaluation of composite GTV based on PET and GTV based on CT are needed. However, in clinical practice, the study showed that using GTV PET alone for treatment planning was similar to using GTVCT for local control and dose distribution was better as a dose to organs at risk significantly decreased. In addition to FDG, pretherapeutic PET could give access to different biological tumoral volumes - thanks to different tracers - guiding heterogeneous dose delivery (dose painting concept) to resistant subvolumes. During radiotherapy treatment, follow-up [18F]FDG PET-CT revealed an earlier and more important diminution of GTV than other imaging modality. It may be a valuable support for adaptative radiotherapy as a new treatment plan with a significant impact on dose distribution became possible. Finally, additional studies are required to prospectively validate long-term outcomes and lower toxicity resulting from the use of PET-CT in treatment planning.
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http://dx.doi.org/10.1097/MNM.0000000000001329DOI Listing
March 2021

Photobiomodulation by a new optical fiber device: analysis of the in vitro impact on proliferation/migration of keratinocytes and squamous cell carcinomas cells stressed by X-rays.

Lasers Med Sci 2020 Nov 9. Epub 2020 Nov 9.

Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Université Lyon 1, Oullins, France.

Photobiomodulation-based (PBM-based) therapies show promising results in mucositis and dermatitis treatment by stimulating wound healing mechanisms such as cell proliferation and migration. The aim of the present study is to investigate the in vitro effects of CareMin650 on the proliferation and migration of two different types of cells, namely cancer and non-cancer cells, with or without X-ray radiation. Study design used PBM through a combination of 0-3-6 J/cm doses-with or without X-ray radiation-on the proliferation and migration capabilities of a keratinocyte cell line (HaCaT) and a squamous cell carcinoma line (SCC61). PBM is delivered by a new woven optical fiber device, namely CareMin650 prototype (light emission by LEDs (light-emitting diodes), peak at 660 nm, irradiance of 21.6 mW/cm). The effectiveness of PBM to increase HaCaT proliferation and migration (with or without X-ray radiation) supports the capability of PBM to favor wound healing. It also highlights that PBM does not provide any anti-radiation effect to previously X-rays radiated SCC (p < 0.001). Such data supports the beneficial effect of PBM delivered by an optical fiber device to heal wounds, without promoting cancer development.
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http://dx.doi.org/10.1007/s10103-020-03185-xDOI Listing
November 2020

Cell-free DNA and circulating TERT promoter mutation for disease monitoring in newly-diagnosed glioblastoma.

Acta Neuropathol Commun 2020 11 4;8(1):179. Epub 2020 Nov 4.

Inserm U1245, Normandie Univ, UNIROUEN, IRON group, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.

The clinical implications of plasmatic cell-free and tumor DNA (cfDNA and ctDNA) are challenging in glioblastoma. This prospective study included 52 consecutive newly diagnosed glioblastoma (n = 49) or gliosarcoma (n = 3) patients treated with concomitant temozolomide and radiotherapy (RT-TMZ), followed by a TMZ maintenance phase. Plasma samples were collected at baseline, before RT-TMZ (pre-RT-TMZ) and at the end of adjuvant TMZ, or at the time of progression in cases of progressive disease (PD). The cfDNA concentration was measured with a fluorometric method, and ctDNA was detected using targeted droplet digital PCR. The main objectives were to analyze the associations between cfDNA and ctDNA measurements during the course of treatment with PD and survival. There was a significant decrease in median cfDNA concentration from baseline to pre-RT-TMZ-19.4 versus 9.7 ng/mL (p < 0.0001)-in the entire cohort. In patients with PD, a significant increase in cfDNA concentration from pre-RT-TMZ to time of PD was observed, from 9.7 versus 13.1 ng/mL (p = 0.037), respectively, while no difference was observed for nonprogressive patients. Neither the cfDNA concentration at baseline nor its kinetics correlated with survival. ctDNA was detected in 2 patients (3.8%) and only in gliosarcoma subtypes.Trial registration ClinicalTrial, NCT02617745. Registered 1 December 2015, https://clinicaltrials.gov/ct2/show/NCT02617745?term=glioplak&draw=2&rank=1 .
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http://dx.doi.org/10.1186/s40478-020-01057-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641818PMC
November 2020

Ceramide-Enriched Membrane Domains Contribute to Targeted and Nontargeted Effects of Radiation through Modulation of PI3K/AKT Signaling in HNSCC Cells.

Int J Mol Sci 2020 Sep 29;21(19). Epub 2020 Sep 29.

Laboratoire de Radiobiologie Cellulaire et Moléculaire, UMR CNRS 5822/IN2P3, IP2I, PRISME, Univ Lyon, Université Lyon 1, Faculté de Médecine Lyon-Sud, 69921 Oullins, France.

We investigated the potential involvement of ceramide-enriched membrane domains in radiation-induced targeted and nontargeted effects using head and neck squamous cell carcinoma with opposite radiosensitivities. In radiosensitive SCC61 cells, the proportion of targeted effects was 34% and nontargeted effects killed 32% of cells. In contrast, only targeted effects (30%) are involved in the overall death of radioresistant SQ20B cells. We then demonstrated in SCC61 cells that nontargeted cell response was driven by the formation of the radiation-induced ceramide-enriched domain. By contrast, the existence of these platforms in SQ20B cells confers a permissive region for phosphatidylinositol-3-kinase (PI3K)/AKT activation. The disruption of lipid raft results in strong inhibition of PI3K/AKT signaling, leading to radiosensitization and apparition of nontargeted effects. These results suggest that ceramide-enriched platforms play a significant role in targeted and nontargeted effects during radiotherapy and that drugs modulating cholesterol levels may be a good alternative for improving radiotherapy effectiveness.
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http://dx.doi.org/10.3390/ijms21197200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582380PMC
September 2020

Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial.

Lancet Oncol 2020 10;21(10):1341-1352

Institut Bergonié, Bordeaux, France.

Background: Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance.

Methods: GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069.

Findings: Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001).

Interpretation: Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events.

Funding: French Health Ministry and Ipsen.
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http://dx.doi.org/10.1016/S1470-2045(20)30454-XDOI Listing
October 2020

Assessment of non-inferiority with meta-analysis: example of hypofractionated radiation therapy in breast and prostate cancer.

Sci Rep 2020 09 22;10(1):15415. Epub 2020 Sep 22.

SAINBIOSE U1059, Equipe DVH, Université Jean Monnet, Saint-Etienne, France.

The aim of this study was to propose a methodology for the assessment of non-inferiority with meta-analysis. Assessment of hypofractionated RT in prostate and breast cancers is used as an illustrative example. Non-inferiority assessment of an experimental treatment versus an active comparator should rely on two elements: (1) an estimation of experimental treatment's effect versus the active comparator based on a meta-analysis of randomized controlled trials and (2) the value of an objective non-inferiority margin. This margin can be defined using the reported effect of active comparator and the percentage of the active comparator's effect that is desired to be preserved. Non-inferiority can then be assessed by comparing the upper bound of the 95% confidence interval of experimental treatment's effect to the value of the objective non-inferiority margin. Application to hypofractionated RT in breast cancer showed that hypofractionated whole breast irradiation (HWBI) appeared to be non-inferior to conventionally fractionated RT for local recurrence. This was not the case for accelerated partial breast irradiation (APBI). Concerning overall survival, non-inferiority could not be claimed for either HWBI or APBI. For prostate cancer, the lack of demonstrated significant superiority of conventional RT versus no RT precluded any conclusion regarding non-inferiority of hypofractionated RT.
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http://dx.doi.org/10.1038/s41598-020-72088-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508968PMC
September 2020

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

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

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

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

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

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

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

Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status.

J Immunother Cancer 2020 08;8(2)

Pathology, University Hospital of Saint-Etienne, Saint-Etienne, France.

Background: Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.

Methods: This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ test, Cramer's V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.

Results: PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.

Conclusion: PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.
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http://dx.doi.org/10.1136/jitc-2020-000597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454240PMC
August 2020

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

Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study.

Lancet Oncol 2020 09 3;21(9):1173-1187. Epub 2020 Aug 3.

CHUV, Service de Radio-oncologie, Bâtiment Hospitalier, Lausanne, Switzerland. Electronic address:

Background: Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck.

Methods: This double-blind, multicentre, randomised, phase 2 study by the French Head and Neck Radiotherapy Oncology Group (GORTEC) was run at 19 hospitals in France and Switzerland. Eligible patients were aged 18-75 years with locoregionally advanced, squamous cell carcinoma of the head and neck (characterised as non-metastatic, measurable stage III, IVa, or IVb [limited to T ≥2, N0-3, and M0] disease), Eastern Cooperative Oncology Group performance status of 0 or 1, a history of heavy tobacco smoking (>10 pack-years) with no previous or current treatment for invasive head and neck cancer, and no previous treatment with inhibitor of apoptosis protein antagonists. Patients were randomly assigned (1:1) to receive oral Debio 1143 (200 mg per day on days 1-14 of 21-day cycles, for three cycles) or oral placebo (20 mg/mL, administered at the same dosing schedule) using a stochastic minimisation technique according to node involvement and primary tumour site, and HPV-16 status in patients with an oropharyngeal primary tumour site. All patients received standard high-dose cisplatin chemoradiotherapy. The primary endpoint was the proportion of patients with locoregional control 18 months after chemoradiotherapy, analysed in the intention-to-treat population (primary analysis), and repeated in the per-protocol population. Responses were assessed according to Response Evaluation Criteria in Solid Tumors (version 1.1). This trial is registered with ClinicalTrials.gov, NCT02022098, and is still active but not recruiting.

Findings: Between Jan 25, 2016, and April 24, 2017, 48 patients were randomly assigned to the Debio 1143 group and 48 to the placebo group (one patient in the placebo group did not receive the study drug and was not included in the safety analysis). Median duration of follow-up was 25·0 months (IQR 19·6-29·4) in the Debio 1143 group and 24·2 months (6·6-26·8) in the placebo group. Locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39-69) of 48 patients in the Debio 1143 group versus 16 (33%; 20-48) of 48 patients in the placebo group (odds ratio 2·69 [95% CI 1·13-6·42], p=0·026). Grade 3 or worse adverse events were reported in 41 (85%) of 48 patients in the Debio 1143 group and in 41 (87%) of 47 patients in the placebo group. The most common grade 3-4 adverse events were dysphagia (in 24 [50%] patients in the Debio 1143 group vs ten [21%] in the placebo group), mucositis (in 15 [31%] vs ten [21%]), and anaemia (in 17 [35%] vs 11 [23%]). Serious treatment-emergent adverse events were recorded in 30 (63%) of 48 patients in the Debio 1143 group and 28 (60%) of 47 in the placebo group. In the placebo group, two (4%) deaths were due to adverse events (one multiple organ failure and one asphyxia; neither was considered to be related to treatment). No deaths due to adverse events occurred in the Debio 1143 group.

Interpretation: To our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients.

Funding: Debiopharm.
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http://dx.doi.org/10.1016/S1470-2045(20)30327-2DOI Listing
September 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

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

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

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

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

Bilateral facial palsy in an older person.

Age Ageing 2020 08;49(5):887-888

Rouen University Hospital, Department of Neurology, 76031 Rouen, France.

Lyme disease is an infectious disease caused by the Borrelia burgdorferi spirochetes and other related species that are transmitted through an infected tick bite. We report the case of an older patient presenting with bilateral facial palsy due to Lyme disease. Multiple non-specific clinical signs preceded facial palsy with falls, fatigue and pain of both legs especially during the night. Our case illustrates the difficulty to diagnose this infectious disease, especially in older patients who have rare outdoor activities and a low risk of tick exposure.
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http://dx.doi.org/10.1093/ageing/afaa082DOI Listing
August 2020

Emergency changes in international guidelines on treatment for head and neck cancer patients during the COVID-19 pandemic.

Oral Oncol 2020 08 24;107:104734. Epub 2020 Apr 24.

Brazilian Group of Head and Neck Cancer/Latin American Cooperative Group - Head and Neck, Brazil; Head and Neck Surgery Department, University of São Paulo Medical School, Sao Paulo, Brazil; Head and Neck Surgery and Otorhinolaryngology Department, A C Camargo Cancer Center, Sao Paulo, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2020.104734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180373PMC
August 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

Local dose analysis to predict acute and late urinary toxicities after prostate cancer radiotherapy: Assessment of cohort and method effects.

Radiother Oncol 2020 Jun 28;147:40-49. Epub 2020 Mar 28.

Univ Rennes, CLCC Eugène Marquis, INSERM, LTSI - UMR 1099, F-35000, Rennes, France.

Purpose: To perform bladder dose-surface map (DSM) analysis for (1) identifying symptom-related sub-surfaces (Ssurf) and evaluating their prediction capability of urinary toxicity, (2) comparing DSM with dose-volume map (DVM) (method effect), and (3) assessing the reproducibility of DSM (cohort effect).

Methods And Materials: Urinary toxicities were prospectively analyzed for 254 prostate cancer patients treated with IMRT/IGRT at 78/80 Gy. DSMs were generated by unfolding bladder surfaces in a 2D plane. Pixel-by-pixel analysis was performed to identify symptom-related Ssurf. Likewise, voxel-by-voxel DVM analysis was performed to identify sub-volumes (Svol). The prediction capability of Ssurf and Svol DVHs was assessed by logistic/Cox regression using the area under the ROC curve (AUC). The Ssurf localization and prediction capability were compared to (1) the Svol obtained by DVM analysis in the same cohort and (2) the Ssurf obtained from other DSM studies.

Results: Three Ssurf were identified in the bladder: posterior for acute retention (AUC = 0.64), posterior-superior for late retention (AUC = 0.68), and inferior-anterior-lateral for late dysuria (AUC = 0.73). Five Svol were identified: one in the urethra for acute incontinence and four in the posterior bladder part for acute and late retention, late dysuria, and hematuria. The overlap between Ssurf and Svol was moderate for acute retention, good for late retention, and bad for late dysuria, and AUCs ranged from 0.62 to 0.81. The prediction capabilities of Ssurf and Svol models were not significantly different. Among five symptoms comparable between cohorts, common Ssurf was found only for late dysuria, with a good spatial agreement.

Conclusion: Spatial agreement between methods is relatively good although DVM identified more sub-regions. Reproducibility of identified Ssurf between cohorts is low.
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http://dx.doi.org/10.1016/j.radonc.2020.02.028DOI Listing
June 2020

Can Comprehensive Geriatric Assessment Predict Tolerance of Radiotherapy for Localized Prostate Cancer in Men Aged 75 Years or Older?

Cancers (Basel) 2020 Mar 9;12(3). Epub 2020 Mar 9.

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, 44800 Saint Herblain, France.

Curative radiotherapy for prostate cancer is common in the elderly. However, concerns about potential toxicity have inhibited access to radiotherapy for this population, for whom preserving quality of life (QoL) is crucial. The primary endpoint was to identify predictors of impaired QoL in men aged 75 years or older treated with curative intent radiotherapy with or without androgen deprivation therapy (ADT) for localized prostate cancer. We prospectively performed comprehensive geriatric assessment (CGA) and administered QoL questionnaires to 208 elderly (>75 years) patients prior to, plus two and six months after, radiotherapy (NCT02876237). The median age of the patients was 77 years (range 75-89). At the start of the study, comorbidities were highlighted in 65% of patients: 23% were depressed, 23% had cognitive impairment, and 16% had reduced independence. At six months, 9% of patients had a consistently decreased QoL (>20 points), and a further 16% had a more moderate reduction (10 to 20 points) in QoL. None of the parameters studied (tumor characteristic, treatment, or oncogeriatric parameters) were predictive of a reduced QoL following radiotherapy. Though co-existing geriatric impairment was common, QoL was maintained for 75% of patients six months after radiotherapy. CGA was poorly predictive of tolerance of prostatic radiotherapy. Geriatric assessments dedicated to quality of life following radiotherapy need to be developed.
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http://dx.doi.org/10.3390/cancers12030635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139355PMC
March 2020

[2019 international oncology news: A compendium].

Bull Cancer 2020 Feb 10;107(2):148-156. Epub 2020 Feb 10.

Centre hospitalier universitaire Giscard d'Estaing, service thérapie cellulaire et hématologie clinique, 58, rue Montalembert, 63000 Clermont Ferrand, France.

Over the past years, planet oncology has kept changing and moving forward. Recent results of important clinical trials are challenging our daily practices. With modesty, the Editorial Board of BulletinduCancer has selected some clinical trials they consider as "must-know about" even if they go beyond our medical fields.
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http://dx.doi.org/10.1016/j.bulcan.2020.01.010DOI Listing
February 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