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Tumour deposits (TD) and extramural venous invasion (EMVI) are key anatomopathology prognostic criteria in rectal cancer. According to the 2018 ESGAR recommendations, they should be included in every MRI report. The present study aimed at identifying pelvic MRI survival prognostic factors in locally advanced rectal cancers before neo-adjuvant treatment, with a focus on EMVI and TD (mrEMVI and mrTD).Between 2010 and 2014, we conducted a retrospective study about 69 patients who underwent a pre-operative radiotherapy for a non-metastatic rectal cancer. All MR images were acquired on machines with a 1.5 or 3.0 Tesla field strength and were interpreted in compliance with the 2018 ESGAR recommendations.Out of the 27 patients who were mrEMVI+ (39.1%), MRF was involved in 77.7% of the cases vs. 33.3% for the mrEMVI- tumours. Fifteen (55.5%) out of the 27 mrEMVI+ tumours were mrTD+. This represents 21.7% of our population. mrEMVI/mrTD+ tumours were more RCT resistant, their downstaging happened in 6.7% of cases. In case of tumour downstaging, DFS increased significantly (P=0.02) unlike OS (P=0.2).The present study supports the fact that both mrEMVI and mrTD status are important pelvic MRI prognostic factors. Future studies could focus on relating mrTD tumours status to pathological results to define if post-RCT downstaging of TD has an impact on OS.

Purpose: The aim of current analyses is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard external beam whole breast radiotherapy (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). Methods and materials: From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers (503 in each arm). Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n=488; APBI: n=490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (> 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy (SLNB; median number: 4 in WBI arm and 5 in APBI), luminal BC. Ductal histology was observed 82%. Only 2% and 1% of patients had grade III and pN(i+) disease. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of: 50Gy in 25fr + 16Gy boost (n=212) or 40Gy in 15fr (n=156) or 42.5Gy in 16fr (n=120), while APBI arm consisted of 38.5Gy or 40Gy in 10fr. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results, evaluated by doctors and by patients, over the entire follow-up. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models adjusted on stratification factors. Results: Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR=0.73 (95% confidence interval: 0.61-0.88); p=0.001, and 3-year cumulative incidence (CI) of severe toxicity at 45% (41-49) in WBI vs 36% (32-40) in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR=0.55 (0.44-0.70), p< 0.001 and 3-year CI at 36% (32-40) in WBI vs 21% (18-25) in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI: cs-HR= 2.10 (1.51-2.91), p< 0.001, and 3-year CI at 8% (5-10) vs 15% (12-19), respectively. When considering cosmetic results according to the investigator, we observed no significant difference between the two arms: cs-HR=1.04 (0.81-1.33), p=0.26 and 3-year probability of remaining with good to excellent cosmetic results at 77% (73-81) in WBI arm and 78% (74-81) in APBI arm. Findings were similar when considering results according to the patient: cs-HR=1.07 (0.85-1.37), p=0.23, and 3-year probability at 74% (70-78) and 75% (70-79), respectively. Conclusions Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We reported increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed. Citation Format: Yazid Belkacemi, Isabelle Gabelle-Flandin, Marie-Cécile Le Deley, Adeline Petit, Philippe Guilbert, Julien Geffrelot, Christian Carrie, Eleonor Rivin Del Campo, Chantal Hanzen, Claire Charra-Brunaud, Isabelle Lecouillard, Nicolas Magne, Agnès Tallet, Nicolas Leduc, Blaha Belgadi, Philippe Fourneret, Alexandre Coutte, Esther Capelo, Franck Darloy, Muriel Garcia Ramirez, Philippe Dudouet, Pierre Clavere, Jean-Philippe Suchaud, Guillaume Auzac, Thomas Lacornerie, Jérôme Lemonnier, Céline Bourgier, Eric Lartigau. Early results of the French multicenter, randomized SHARE trial comparing whole breast irradiation versus accelerated partial breast irradiation in postmenopausal women with early-stage breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-05.

To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score.The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities.Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population.These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.

Background: Acute radiodermatitis (ARD) is a common side effect of breast cancer radiotherapy. It includes erythema, burning sensation, swelling, epilation, desquamation, ulceration, or necrosis. So far, there has been no consensus about the best practice in preventing /treating ARD. Objectives: This is the first study to assess the efficacy of topical phenytoin in the prevention and treatment of ARD. Methods: This prospective randomized double-blind trial was a placebo-controlled study. A total of 70 patients with breast cancer were included. They were referred for breast radiotherapy after radical mastectomy. Patients were randomly assigned to either the topical phenytoin or placebo group. Both ointments were applied twice and daily on affected areas of the chest. Acute radiodermatitis was evaluated every week, for 5 weeks, during radiotherapy. A blinded-to-treatment physician used the “(radiation therapy oncology group) RTOG dermatitis scoring” to do so. Results: During the first 3 weeks, ARD was neither severe (RTOG < 2) nor statistically different between the two treatment groups (P > 0.05). However, after the 3rd week, the ARD score was lower in phenytoin group than in the placebo group (P < 0.05). Conclusions: Phenytoin topical ointment could postpone the occurrence and/or decrease the severity of ARD in patients with breast cancer.

International audience; Introduction: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Methods: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed.Results: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms.Conclusions: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.

International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.

Based on histopathology, Edinburgh diagnostic criteria were proposed to consider a nontraumatic intracerebral lobar hemorrhage (ICH) as related to cerebral amyloid angiopathy (CAA) using the initial computed tomography (CT) scan and the APOE genetic status. We aimed to externally validate the Edinburgh prediction model, excluding the APOE genotyping and based on the modified Boston criteria on the MRI for CAA diagnosis METHODS: We included patients admitted for spontaneous lobar ICH in the emergency department between 2016 and 2019 who underwent noncontrast CT scan and MRI. According to the MRI, patients were classified into the CAA group or into the non-CAA group in the case of other causes of ICH. Two neuroradiologists, blinded to the final retained diagnosis, rated each radiological feature on initial CT scan described in the Edinburgh study on initial CT scan RESULTS: A total of 102 patients were included, of whom 36 were classified in the CAA group, 46 in the non-CAA causes group and 20 of undetermined cause (excluded from the primary analysis). The Edinburgh prediction model, including finger-like projections and subarachnoid extension showed an area under receiver operating characteristic curves (AUC) of 0.760 (95% confidence interval, CI: 0.660-0.859) for the diagnosis of CAA. The AUC reached 0.808 (95% CI: 0.714-0.901) in a new prediction model integrating a third radiologic variable: the ICH cortical involvement.Using the Boston MRI criteria as a final assessment, we provided a new external confirmation of the radiological Edinburgh CT criteria, which are directly applicable in acute settings of spontaneous lobar ICH and further proposed an original 3‑set model considering finger-like projections, subarachnoid extension, and cortical involvement that may achieve a high discrimination performance.

Summary 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.

Objective The aim of this study was to determine the success rate of sEEG in locating the epileptogenic zone (EZ) in patients with pharmaco-resistant epilepsy. Secondary objectives were to analyze sEEG-related morbidity and outcomes for post-sEEG thermocoagulation and cortical resection. Methods Data were collected on 49 sEEGs from 46 consecutive patients between 2010 and 2018. Following sEEG, either resective or palliative surgery with vagus nerve stimulation was performed. In 8 patients, EZ thermocoagulation was performed before EEG leads were withdrawn. Outcomes were collected based on the Engel and ILAE outcome scales. Results sEEG was contributive in 45 of 49 recordings, with a success rate of 92% in locating the EZ. Minor complications, such as transient neurologic deficit and electrode implantation failures, occurred in 6%. One major complication occurred, with death due to atypical late hematoma. Thermocoagulation was performed in 8 patients and stopped or significantly reduced seizure frequency in 7 (88%). Outcome of surgical resection (n = 33) was good, with 20 (61%) seizure-free patients and 32 (97%) with definite improvement. Conclusions Our findings suggest that sEEG is an effective technique for EZ location in patients with drug-resistant epilepsy. sEEG was contributive in up to 92% of patients, allowing thermocoagulation and/or surgical resection that resulted in seizure-freedom in two-thirds and seizure-reduction in one-third of cases. This study highlights the need for strict selection of implantation candidates, with strong initial hypothesis as to EZ location.

Simple Summary A cohort of 123 women with stage I-II breast cancer enrolled in a prospective clinical trial of adjuvant radiotherapy who were followed for over 10 years. Year 2020 was associated with excess mortality. The number of deaths (n = 5) in that single year represented a third of all deaths (n = 15) in the full decade before. There was in that year a significant increase in lung-heart toxicity and a significant decline in lung-heart function as measured by left ventricular ejection fraction, forced vital capacity and carbon-monoxide diffusing capacity. We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.

International audience

Once again this year, the Editorial Board presents here a summary of the most important advances in treatment and patient care in oncology over the past year. Some of the most important results in breast and gynecological cancers (endometrium and cervix), lung, brain, urologic and digestive cancers. Are also presented progresses in hematological malignancies, pediatric oncology, and of course supportive care essential for our patients.

Prostate cancer is the most common men cancer in France. Continuous progress in oncology led to develop robot-assisted Radical Prostatectomies (rRP) and robot-assisted stereotactic body radiotherapy (rSBRT). The present study aims at comparing economic and clinical impacts of prostate cancer treatments performed either with rSBRT or rRP in France. A Markov model using TreeAge Pro software was chosen to calculate annual costs; utilities and transition probabilities of localized prostate cancer treatments. Patients were eligible for radiotherapy or surgery and the therapeutic decision was a robot-assisted intervention. Over a 10-year period, rSBRT yielded a significantly higher number of quality-adjusted life years than rRP (8.37 vs 6.85). In France, rSBRT seemed more expensive than rRP (€19,475 vs €18,968, respectively). From a societal perspective, rRP was more cost-saving (incremental cost effectiveness ratio = €332/QALY). The model was sensitive to variations of costs of the initial and recurrence state in one-way sensitivity analyses. Robot-assisted stereotactic body radiotherapy seems more cost-effective than Radical Prostatectomy in terms of QALY despite the slightly higher initial cost due to the use of radiotherapy. It would be interesting to conduct comparative quality of life studies in France over longer periods of time.

The Nectin cell adhesion protein 4 (Nectin-4) is overexpressed in multiple human malignancies. Such aberrant expression is correlated with cancer progression and poor prognostic. Nectin-4 has emerged as a potential biomarker and promising targeted therapy. This review aimed to gather the current state of the literature about Nectin-4 relevance in preclinical tumor models and to summarize its clinical relevance regarding cancer. A systematic assessment of literature articles was performed by searching in PUBMED (MEDLINE) from the database inception to May 2021, following PRISMA guidelines. Preclinical models unanimously demonstrated membrane and cytoplasmic location of the Nectin-4. Furthermore, Nectin-4 was overexpressed whatever the location of the solid tumors. Interestingly, a heterogeneity of Nectin-4 expression has been highlighted in bladder urothelial carcinoma. High serum Nectin-4 level was correlated with treatment efficiency and disease progression. Finally, generated anti–drug-conjugated targeting Nectin-4 induced cell death in multiple tumor cell lines. Nectin-4 emerges as a promising target for anticancer drugs development because of its central role in tumorigenesis, and lymphangiogenesis. Enfortumab vedotin targeting Nectin-4 demonstrated encouraging results and should be extended to other types of solid tumors.

Purpose: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. We carried out a study about SBRT in patients with ultra-central lung tumours treated in our Cancer Centre. Our objectives were to assess toxicities, local control (LC) rate and survival data.Methods: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose PTV (planning target volume) overlapped one of the following organs at risk (OAR): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. Patients with primary or secondary tumour were enrolled in the study.Results: Median follow-up was 25 months. Two patients (2.7%) showed grade 3 toxicity. No grade 4 or 5 toxicity was observed. Eleven per cent of patients experienced primary local relapse. Local control rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival (PFS) was 12 months. Median overall survival (OS) was 31 months. Conclusions: SBRT for ultra-central tumours remains safe and effective. Thus, SBRT can be considered to be well tolerated as long as protecting organs at risk remains treatment planning priority. Besides, as the results of ongoing prospective trial have not been published yet, SBRT for ultra-central tumours should be performed with caution.

2046 Background: The prediction of the relapse pattern is an important issue in glioblastoma for personalized approach. Molecular factors, such as MGMT promoter methylation, influence relapse in- or out-field of the initial radiotherapy volume. Recently, a recurrent mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor ( EGFRA289mut) has been associated with a more infiltrative phenotype in glioblastoma. The primary objective of the present study was to explore the impact of EGFRA289mut on the pattern of relapse after a chemo-radiotherapy based treatment of patients suffering from glioblastoma. Methods: An ancillary study from a monocentric prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFRA289 status (mutated versus wild-type). Primary endpoint was the overlap score (varying from 0 to 1) between initial irradiated tumor volume (Vinit) and relapse volume (Vr). Vinit was the initial 95% isodose of the radiotherapy and Vr was delineated using the enhanced MRI T1-weighted part of the relapse tumor. Secondary endpoints explored the impact of other EGFR extracellular mutations, EGFR amplification and EGFRvIII on the relapse pattern, as well as the impact of EGFRA289mut on survival. EGFR alterations were identified using next-generation sequencing or droplet-digital PCR based methods on formalin-fixed paraffin-embedded samples collected at initial diagnosis. Results: One hundred patients were included: 11% of the population had EGFRA289mut glioblastoma (n = 11/100). EGFRA289mut glioblastomas had a relapse pattern more marginal compared to EGFRA289wt glioblastomas: a mean overlap score Vinit/Vr of 0.78 was observed in the EGFRA289mut group versus 0.94 in the EGFRA289wt group (p = 0.021). The proportion of EGFR A289mut glioblastomas in the outfield relapse (overlap score < 0.8) has a trend to be higher than in the infield relapse (overlap score > 0.8): 25% (n = 2/8) versus 9.8% (n = 9/92) for the EGFRA289wt population, p = 0.21. Neither EGFR amplification nor EGFRvIII did influence overlap score Vinit/Vr. In our population, EGFRA289mut did not influence survival. Conclusions: EGFR A289mut influences the relapse pattern in a population of patients suffering from glioblastoma. The role of EGFRA289mut as a decision-making biomarker for personalized radiotherapy should now be investigated in dedicated clinical trial. Clinical trial information: NCT02617745.

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.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

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 RecoveThis 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 RecoveBaseline characteristics including age, and BMI had no significant difference between groups. The Recover group patients experienced significantly less severe dermatitis compared to the controls (p0.001). 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 5Our results indicate that Recove

3D-FLAIR sequences with delayed acquisition after contrast medium injection have demonstrated new insights into blood-labyrinthine barrier (BLB) abnormalities in various diseases. The aim of this study was to assess the BLB in patients referred with unilateral acute vestibular syndrome (UAVS). In this retrospective multicenter imaging study, we performed 3D-FLAIR and steady-state free precession (SSFP) sequences 4 h after contrast medium administration in 26 healthy volunteers and in 30 patients with UAVS. Two radiologists, blinded to the clinical data, independently assessed the asymmetrical enhancement of the labyrinthine structures and the vestibular nerve on 3D-FLAIR sequences, and the signal of the labyrinthine structures on SSFP sequences. Inter-reader agreement tests were performed. An asymmetrical enhancement of the semicircular canals was observed in 26 out of 30 ears (86.6%, p

Objectives: The main standard of care for locally advanced cervix carcinoma (LACC) is radiochemotherapy (RCT) followed by brachytherapy. A surgical approach may still be discussed based on pelvic MRI-derived residual tumour evaluation. As no interobserver agreement study has ever been conducted to our knowledge, the aim of the present study was to report on pelvic MRI accuracy and interobserver agreement in LACC. Methods: We carried out a retrospective study in a French university hospital. Medical records of all consecutive patients treated with curative intent for LACC by RCT followed by brachytherapy and completion pelvic surgery between January 2014 and January 2020 were reviewed. Local response was assessed through pelvis MRI and histological analysis after completion surgery. MRI data were independently evaluated by two radiologists with varying experience. The two main interobserving criteria we used were complete response and residual tumour. Results: 23 patients fulfilled the inclusion criteria. Agreement between the junior and senior radiologist was moderate to strong. Indeed, regarding main criteria, κ was 0.65 for complete response and 0.57 for residual tumour. Interestingly, the present study shows a lower sensitivity whatever the radiologists than in the international literature. Conclusion: The present study highlights a low interobserver variability regarding pelvic MRI in the assessment of RCT followed by brachytherapy in LACC. Yet, sensitivity was lower than in literature. Advances in knowledge: Radiology is part of treatment decision-making, the issue of heterogeneity regarding radiologists’ training and experience to cancer (sensitivity and specificity) turns essential, so does MRI accuracy.

Cerebral venous thrombosis (CVT) is an underdiagnosed complication of head trauma. To date, initiation of anticoagulation is still a matter of debate because of the risk of worsening traumatic hemorrhage. This report describes a case series of five patients admitted for head injury complicated by CVT. The main associated radiological signs were skull fractures crossing the venous sinus and adjacent traumatic hematoma. In four patients, anticoagulation was introduced within 48-72h of CVT diagnosis, with no subsequent hemorrhagic complications. The present report and data from the literature raise the question of systematic additional venoscans when confronted by associated radiological features of post-traumatic CVT. The safety of anticoagulation in selected patients is also discussed.

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.

Background Spinal myxopapillary ependymoma (SP-MPE) is a subgroup of ependymomas in which after initial gross tumor resection, recurrences occur in more than half of the patients. Anaplastic transformation may also occur and contributes to intraneural and extraneural metastatic dissemination. Extraneural metastases from SP-MPE are rare and worsen the prognosis. In this situation, the noninvasive detection of recurrent somatic mutations in the circulating tumor DNA (ctDNA) from plasma is challenging. Telomerase-reverse transcriptase gene promoter (TERTp) mutation has been identified in a subset of ependymomas with aggressive behavior. Case Description We report on a patient with TERTp mutated SP-MPE presenting with an extraneural anaplastic metastatic dissemination after iterative local recurrences. From the initial SP-MPE to pleural anaplastic lesion, TERTp C228T mutation was present with allele frequency varying from 33% to 39%. Interestingly, TERTp mutation was also detected by droplet digital polymerase chain reaction in the plasma with a frequency of 2.1% at the time of pleural metastases, highlighting that ctDNA is released in plasma of patients suffering from SP-MPE with extraneural metastatic dissemination. Conclusions Despite the rarity of this evolution, plasmatic liquid biopsy appears to be a useful diagnostic and follow-up tool in a subset of primary brain tumors.

Introduction A l’ere de la thrombectomie mecanique (TM), l’utilite de la thrombolyse intraveineuse (TIV) fait debat. Peut-on se passer de la TIV en cas d’occlusion arterielle cerebrale proximale lorsque l’on a un acces rapide au plateau de neuroradiologie interventionnelle (NRI) ? Objectifs Comparer le pronostic fonctionnel a 3 mois des patients victimes d’un infarctus cerebral (IC) avec occlusion d’un gros vaisseau traites par therapie combinee (TIV et TM) versus TM seule. Patients et methodes Etude descriptive, retrospective au CHU de Rouen portant sur les IC survenus entre 11/2011 et 06/2019, directement admis au CHU. Inclusion des IC avec une occlusion proximale eligibles a une TM, associee ou non a une TIV. Comparaison du pronostic fonctionnel des patients traites par therapie combinee versus TM seule. Inclusion des patients ayant recanalise suite a la TIV seule. Critere de jugement principal : score de Rankin modifie (mRS) a 3 mois (bonne evolution clinique : mRS ≤ 2). Resultats Au total, 265 patients ont ete inclus :115 ont recu une therapie combinee et 138 une TM seule. Douze patients ont recanalise suite a la TIV seule. Benefice a la therapie combinee sur le pronostic fonctionnel a 3 mois par rapport a la TM seule (p = 0,006). Taux de deces superieur dans le groupe traite par TM seule (p = 0,048), et absence de difference significative concernant le taux de transformation hemorragique cerebrale, de nouvelles ischemies cerebrales ni du score de recanalisation TICI. Discussion La TIV pourrait faciliter la lyse du thrombus et ainsi le geste de TM, raccourcir les delais de recanalisation sans majorer le risque hemorragique cerebral. Conclusion Nos resultats suggerent de poursuivre la realisation de la TIV lorsqu’elle est indiquee, en amont de la TM, comme recommande actuellement. Des etudes randomisees complementaires sont neanmoins necessaires et en cours actuellement.

International audience; Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.

Objective Optimal ventricular catheter positioning is able to reduce the risk of catheter dysfunction, and subsequently the risk of multiple revision surgery. The objective of our study was to compare the proportion of optimal ventricular catheter placements in a cohort of patients operated for ventriculoperitoneal (VP) shunt between a free-hand group and a neuronavigated group. Patients and methods Twenty patients with hydrocephalus requiring VP shunt were prospectively included in this study. Patients were divided into two groups; the ventricular catheter was positioned using free-hand method (n = 10) or magnetic navigation system (n = 10). For the two groups, clinical baseline characteristics, etiology of hydrocephaly and initial ventricular size were assessed. The main judgment criterion was the proportion of optimal catheter placements defined by the presence of all catheter holes in the ventricle, evaluated on post-operative CT scan. Results There was no initial difference between the two groups in terms of hydrocephalus etiology or initial ventricular size. The number of optimal catheter placements was 6/10 in the neuronavigated group versus 1/10 in the free-hand group (p Conclusion In patients suffering from hydrocephaly, the use of an electromagnetic neuronavigation system for ventricular catheter placement significantly improved the proportion of optimal catheter placements. Long-term follow-up is necessary to evaluate the number of revision surgeries and the cost in each group.

Purpose Due to the increased protein concentration in the perilymph liquid, FIESTA-C has recently been proposed to assess endolymphatic spaces without administration of contrast media in patients with vestibular schwannoma. The aim of this study was to assess whether vestibular endolymphatic space dilatation, as evaluated with 3D-FIESTA-C sequences, is related to the degree of hearing loss in patients with schwannoma. Materials and methods In this retrospective study (IRB 5995), we performed 3D-FIESTA-C sequences in 32 patients with schwannoma, as diagnosed on the basis of typical image findings. Two radiologists independently checked the visualization and evaluated the volume of the utricle and saccule. Pearson and Spearman tests were used to explore the correlation between the volume of the tumor, the volume of the vestibular endolymphatic space and the degree of hearing loss – as evaluated with the levels of pure-tone average (PTA) and speech recognition threshold (SRT). Results The endolymphatic space can be evaluated in 72% (23 out of 32 patients) of patients with schwannoma on non-contrast 3D-FIESTA-C sequences. The mean saccular, utricular and tumor volume were 3.17 mm3, 14.55 mm3 and 1.74 cm3 respectively. There was a significant correlation between the volume of the utricle and the degree of hearing loss as evaluated with the levels of PTA (p = 0.015) and SRT (p = 0.004). There was no significant correlation between the saccular and tumor volumes and the degree of hearing loss. Conclusion The volume of the utricle in schwannoma patients is related to the degree of hearing loss.

Vegetation indices calculated on multispectral images have been used for quantify the health and status of vegetation. Images used for these studies were been obtained with Landsat 8 satellite, these images represent high cost for low and middle budget organization. This work present the methodology for develop an open source multispectral camera array for vegetation analysis. This system has been built in base of open source devices such as Raspberry Pi Linux Computer on Module, and open source libraries like OpenCV. Also, the entire code, schematics and diagrams have been released with open source licenses.