Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.

PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases. METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC. RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed. CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.

Type II endometrial cancer: Incidence, overall and disease-free survival in Martinique.

BACKGROUND AND STUDY AIMS: In Martinique, about 33 new cases of endometrial cancer are diagnosed per year with a high mortality rate (world standardised rate of 4.9/100,000 versus 2.3/100,000 in mainland France). The present study aimed to determine the incidence and mortality of type I and type II endometrial cancers (ECs), their overall survival (OS) and disease-free survival (DFS) between 2012 and 2016. PATIENTS AND METHODS: This retrospective observational cohort study used data from the Martinique Cancer Registry (MCR). 191 patients with corpus uterine cancer were extracted between 2012 and 2016. Patients with either endometrioid endometrial carcinoma (EEC), uterine papillary serous carcinomas (UPSC), uterine clear cell carcinomas (UCCC) or uterine carcinosarcomas (UCS) were included. All other uterine cancers were excluded. RESULTS: Among the 163 included patients, 97 (60%) were type I and 66 (40%) were type II. The standardized incidence rate is 4.50/100,000 for type I vs. 2.66/100,000 for type II. Three years DFS for all types, type I and type II was 81.5% [74.2-86.9], 84.9% [75.4-91] and 76.7% [63.8-85.5] respectively. The five-years OS for all types, type I and type II was 47.0% [38.9-54.7] vs. 58.8% [47.3-68.5] vs. 22.8% [15.0-37.7] respectively. CONCLUSIONS: In Martinique, we report a high proportion of type II ECs, which has a poor prognosis with few treatment options.

Recove® burn ointment for managing acute radiodermatitis in patients with breast cancer: A double blind randomized controlled trial.

Background: Radiodermatitis is the most common complication of radiotherapy. There is no gold standard for managing the radiodermatitis. This study aimed to evaluate the effect of topical Recove® burn ointment; basically compounded of sesame oil, camphor, and zinc oxide; in preventing acute radiodermatitis. Methods: This double blind RCT (IRCT No.: 201204047136N2) was performed on 71 patients that referred for radiotherapy after mastectomy to Shahid Rajaee Hospital (Babolsar-Iran) during 2013-2017. Patients were allocated into 2 groups; 34 in control group and 37 in Recove® group. Patients applied the ointment 2 times a day, before every radiation therapy session for 5 weeks. The radiation oncologist assessed the severity of dermatitis weekly for 5 weeks and graded it from 0 to 4 according to the RTOG criteria. Results: Baseline characteristics including age, and BMI had no significant difference between groups. The Recover group patients experienced significantly less severe dermatitis compared to the controls (p<0.001). None of the patients in Recove® group encountered more than grade 2 of RTOG criteria, however, in the control group, 4 (12.9%) patients experienced grade 3 of RTOG and 3 (9.7%) patients developed grade 4 of RTOG at the end of the 5th week. Conclusion: Our results indicate that Recove® ointment significantly reduces the severity of acute radiodermatitis.

Providing Patients with Locally Advanced Cervical Cancer Access to Brachytherapy: Experience from a Referral Network for Women Treated in Overseas France.

Image-guided adaptive brachytherapy (IGABT) is part of the standard of care for locally advanced cervical cancer (LACC). Access to IGABT is limited in many regions, thus leading to treatment care disparities. We report the experience of a referral network for women with LACC between radiotherapy facilities in Overseas France and Gustave Roussy. This is a retrospective review of patients with LACC referred to Gustave Roussy, for pulsed-dose-rate (PDR) image-guided adaptive BT after initial radiation therapy in the French overseas between 2014 and 2021. Sixty-four patients were eligible to receive IGABT. Overall treatment time (OTT) was 60.5 days (IQR: 51−68.5). The median follow-up time was 17 months. At two years, estimated probabilities of LC, progression-free survival, and overall survival (OS) were 94.6% (95% CI: 88.9−100.0%), 72.7% (95% CI: 61.1−86.5%), and 82.5% (95% CI: 72.0−94.5%). In multivariable analysis, a D90CTVHR < 85GyEQD2 and a CTVHR volume > 40 cm3 were significant for poorer PFS (p = 0.001 and p = 0.009, respectively) and poorer OS (p = 0.004 and p = 0.004). The centralization of this advanced technique to expert centers requires a well-defined workflow and appropriate dimensioning of resources to minimize OTT.

Preservation of organs related to future sexual function during prostate stereotactic body radiotherapy: feasibility analysis through a re-optimization process.

Preserving the quality of life and sexual function of patients with a localized prostate cancer remains a challenge for physicians and a major issue for patients. The present study aimed at demonstrating the feasibility of a dosimetric preservation of the sexual organs during prostate stereotactic radiotherapy planning. Patients from a single centre were retrospectively included in the RPAH-2 trial and randomized in Arm B if they presented with either a low- or intermediate- risk prostate cancer. A 37.5Gy in 5 fractions stereotactic body radiotherapy was delivered on the prostate gland. The corpus cavernosum, penile bulb and internal pudental arteries were retrospectively delineated before a re-optimization process. During this process, RPAH-2 trial dose constraints were respected on Gross Tumor Volume (GTV), Planning Target Volume and usual organs at risk. Pre-defined dose setting delivered to corpus cavernosum, penile bulb and internal pudental arteries were collected and compared before and after the re-optimization process. Nine patients were included in the study. A decrease of the median of each investigated dose setting (except D90% for corpus cavernosum) was reported after the re-optimization for corpus cavernosum, penile bulb and internal pudental arteries. Our study demonstrated the feasibility of a dosimetric preservation of structures considered as relevant to preserve sexual function after prostate stereotactic radiotherapy.

Dose to pelvic lymph nodes in locally advanced cervical cancer during high-dose-rate brachytherapy with tandem-ring applicators.

Purpose: The present study aimed to assess the correlation between dose to pelvic lymph nodes and to point B with tandem-ring (TR) applicators for intra-cavitary brachytherapy treatment of locally advanced cervical cancer. Material and methods: Cervical cancer patients treated at brachytherapy department of Lucien Neuwirth Cancer Center, from 2015 to 2018, were included. Target delineation was performed in compliance with GEC-ESTRO guidelines. Revised American Brachytherapy Society (ABS) point A was determined (ARN (right) and ALN (left)) as well as Manchester point B. Prescription dose was 25-35 Gy in 5 fractions. Pelvic lymph nodes were delineated, then dose to points A and B, and dose-volume histogram (DVH) parameters of delineated lymph nodes were extracted. Significant relationships or correlations between lymph nodes reference points, dosage to points B, and their DVH parameters were investigated. Results: The mean dose and mean percentage of the prescription dose to the left and right points B were 4.6 ±0.18 Gy and 82.08 ±0.72%, respectively. Pearson correlation coefficient R = 0.81 (p-value = 0.00) between dose to ARN and ALN points and prescription dose was obtained. Negative correlation between CTVHR volume and difference between French and ABS prescription points was found. Conclusions: Dose to point B can be a moderate surrogate for maximum, minimum, and median dose to the internal iliac and presacral lymph node, but cannot be for maximum dose to the obturator lymph node. Points B cannot be a reliable substitute for common and external iliac chains.

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

Radioresistance and genomic alterations in head and neck squamous cell cancer: Sub-analysis of the ProfiLER protocol.

BACKGROUND: Genome analysis could provide tools to assess predictive molecular biomarkers of radioresistance. METHODS: Head and neck squamous cell carcinoma patients included in ProfiLER study and who underwent a curative radiotherapy were screened. Univariate and Cox multivariate analyses were performed to explore the relationships between molecular abnormalities, infield relapse and complete tumor response after radiation. RESULTS: One hundred and forty-three patients were analyzed. PIK3CA mutation and genomic instability of MAP kinases pathway were found to be prognostic factors of loco-regional relapse in multivariate analysis with respectively HR 0.33, 95% CI 0.13-0.83, p = 0.005 and HR 0.61, 95% CI 0.38-0.96, p = 0.025. Instability of apoptosis pathway was found to be a prognostic factor of complete response after radiotherapy with HR 0.24, 95% CI 0.07-0.88, p = 0.04. CONCLUSION: This sub analysis suggests that PIK3CA mutation, variation of copy number of MAP kinases and apoptosis pathways play a significant role in the radioresistance phenomenon.

Focus on the expected quality of reporting in SBRT/radiosurgery prospective studies: how far have we come in 30 years?

OBJECTIVES: We aimed at describing and assessing the quality of reporting in all published prospective trials about radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). METHODS: The Medline database was searched for. The reporting of study design, patients' and radiotherapy characteristics, previous and concurrent cancer treatments, acute and late toxicities and assessment of quality of life were collected. RESULTS: 114 articles - published between 1989 and 2019 - were analysed. 21 trials were randomised (18.4%). Randomisation information was unavailable in 59.6% of the publications. Data about randomisation, ITT analysis and whether the study was multicentre or not, had been significantly less reported during the 2010-2019 publication period than before (respectively 29.4% vs 57.4% (p < 0.001), 20.6% vs 57.4% (p < 0.001), 48.5% vs 68.1% (p < 0.001). 89.5% of the articles reported the number of included patients. Information about radiation total dose was available in 86% of cases and dose per fraction in 78.1%. Regarding the method of dose prescription, the prescription isodose was the most reported information (58.8%). The reporting of radiotherapy characteristics did not improve during the 2010 s-2019s. Acute and late high-grade toxicity was reported in 37.7 and 30.7%, respectively. Their reporting decreased in recent period, especially for all-grade late toxicities (p = 0.044). CONCLUSION: It seems necessary to meet stricter specifications to improve the quality of reporting. ADVANCES IN KNOWLEDGE: Our work results in one of the rare analyses of radiosurgery and SBRT publications. Literature must include necessary information to first, ensure treatments can be compared and reproduced and secondly, to permit to decide on new standards of care.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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 in vitro and in vivo. 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.

[Docetaxel for octogerian metastatic castration-resistant prostate cancer patient: A multicentric ten years' experience]. / Docétaxel dans le cancer de prostate métastatique résistant à la castration chez l'octogénaire : analyse multicentrique de dix ans de pratique.

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.

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

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, IGF1Rα, IGF1Rß, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rß, 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.

[Stereotactic body radiotherapy: Passing fad or revolution?] / Radiothérapie stéréotaxique : changement de monde ou effet de mode ?

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.

[From bench to bedside for new treatment paradigms in chordomas: An update]. / Depuis la recherche translationnelle jusqu'aux nouveaux paradigmes thérapeutiques : mise à jour des données dans les chordomes.

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.

[Radiotherapy and immune suppression: A short review]. / Radiothérapie et immunosuppression : synthèse de la littérature.

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.