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Resume Le recours a un ou plusieurs confreres est une pratique medicale habituelle et l’exercice solitaire de la cancerologie est revolu mais il doit encore evoluer pour mieux repondre aux attentes des patients. Le patient et eventuellement ses proches doivent etre associes aux demarches diagnostiques et therapeutiques. L’interet du patient et le secret medical sont toujours a respecter. Le praticien radiotherapeute, doit accepter et aider un patient pour la demande d’un second avis. Les reunions de concertation pluridisciplinaires (RCP) de recours, l’acces aux techniques innovantes, a des protocoles de recherches, a une prise en charge prenant en compte les specificites des patients telle que la population des adolescents et jeunes adultes sont autant d’outils qu’il faut savoir connaitre et manier en respectant les attentes des patients, la pluri-professionnalite et la confraternite. Parfois, lors d’un diagnostic initial, il ressort de tous les avis que l’abstention therapeutique est la meilleure option a proposer. L’information adaptee et une bonne communication sont alors les atouts pour faire comprendre et accepter au patient que la seule surveillance active ne lui fera pas courir de risque carcinologique tout en preservant sa qualite de vie. Dans le cas d’une recidive, une radiotherapie de rattrapage meme realisable doit etre profondement reflechie et toujours discutee si possible au sein de reseaux dit de tumeurs rares. Dans des situations peu frequentes ou complexes savoir passer la main a des centres experts peut aussi etre salutaire. Les modalites de la radiotherapie se sont diversifiees avec les avancees technologiques et ne sont a present plus qu’exceptionnellement disponibles sur un meme site. Parmi ces techniques de recours, on retrouve la protontherapie, la contactherapie, la radiotherapie stereotaxique avec tracking ou la curietherapie. Chaque radiotherapeute doit connaitre les benefices en survie, controle local ou preservation fonctionnelle de ces modalites ainsi que leurs organisations specifiques qui en facilitent l’adressage.

International audience; Background: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy.Methods: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP).Results: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found.Conclusion: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.

Càncer de cap i coll; Radioteràpia; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Cáncer de cabeza y cuello; Terapia de radiación; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Head and Neck Cancer; Radiation Therapy; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Purpose Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. Methods and Materials A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. Results In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

The rise of services sectors is a characteristic feature in developed economies. Thanks to a unique dataset for Belgianmanufacturing firms over the years 1997-2013, we provide a description of this phenomenon, focusing on manufacturing firms that provide services. This phenomenon is highly heterogeneous between and within sectors. In particular, the relationship between servitisation and firm efficiency can be increasing, decreasing or U-shaped according to the sector, pointing to different strategies for turning to services provision. In low-tech sectors, both high-efficiency and low-efficiency firms servitise more ; in high-tech sectors, high-efficiency firms servitise the most, while low-efficiency firms are more servitised in medium-tech sectors., L’importance croissante des secteurs des services est une des tendances des économies développées. Grâce à une base de données couvrant les entreprises belges sur la période 1997-2013, nous décrivons ce phénomène de tertiarisation, en particulier celui des entreprises industrielles qui fournissent des services. Une grande hétérogénéité prévaut, tant entre qu’à l’intérieur des industries manufacturières. Ainsi ce ne sont pas nécessairement les entreprises manufacturières les plus performantes qui ont recours à la tertiarisation. Certes la relation entre tertiarisation et efficience peut être croissantemais elle peut être également décroissante ou en forme de U, selon le secteur. Dans les secteurs à faible intensité technologique, ce sont les firmes peu efficaces et les firmes très efficientes qui se tertiarisent le plus. Dans les secteurs à forte intensité technologique, ce sont les entreprises les plus efficientes qui recourent à la tertiarisation de leurs activités tandis que dans les secteurs à intensité technologique moyenne ce sont les entreprises les moins efficientes qui y recourent., Blanchard Pierre, Fuss Catherine, Mathieu Claude. Manufacturing Firms as Services Providers: What the Belgian Data Show. In: Économie & prévision, n°217, 2020. pp. 117-140.

Purpose: To evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and Materials: OPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ≥2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. Results: In the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P

TPS434 Background: At diagnosis, 10 to 15% of testicular pure seminomas have a stage II defined by the presence of retroperitoneal lymph node metastases. The optimal choice of treatment modalities are associated with excellent efficacy but also acute and late toxicities. De-escalating treatment for seminoma patients with stage IIb, IIc and III and good prognosis according to IGCCCG (International Germ Cell Cancer Collaborative Group) based on negative FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) after 2 cycles of EP (etoposide, cisplatine) chemotherapy seems feasible and safe according to SEMITEP cohort 2 results (Loriot Y, and al GETUG SEMITEP Trial: Eur Urol. 2022 Aug;82(2):172-179). Serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers. The aim of the study NCT05529251 is to propose a new therapeutic approach for the stages IIa/IIb. Methods: This phase II, multicenter, prospective, randomized, non-comparative, de-escalation study will include patient with primary testicular seminomatous germ cell tumor with stage IIa/IIb < 3 cm in largest diameter seminoma, histologically proved after orchiectomy and good prognosis according to IGCCCG and LDH (Lactate DesHydogenase) < 2.5 x Upper Limit of Normal (ULN). They must have progressive disease and no prior treatment with radiotherapy or chemotherapy. In case of negative week-3 (after 1 EP cycle) PET-scan, patients will be randomized according to 2 arms ARM A: Boost of radiotherapy 20 to 30 Gray (Gy); ARM B Carboplatin AUC7 chemotherapy. In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C). Primary outcome will include progression-free rate at 36 months. Secondary Outcome Measures will be serum level of miRNA M371, correlation with response to treatments and PET scan results, overall survival (OS), quality of life and tolerance to treatment. Blood samples (miRNA-M371) will be collected at screening, at the time of randomization before second cycle of chemotherapy or radiotherapy, at the end of treatment and at relapse. Enrollment has started in October 2022. A total of 90 patients will be included in the interventional study, leading to approximately 60 patients with negative FDG-PET randomized. Clinical trial information: NCT05529251 .

BACKGROUND The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors. METHODS A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported. RESULTS The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non-responders in terms of 5-year OS (35.1% vs 13.3%, P

Introduction: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this individual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS). Patients and methods: Eligible trials should have closed to accrual before 2016 and compared neoadjuvant chemotherapy and surgery (CS) to surgery alone. All relevant published and unpublished trials were identified via searches of electronic databases, conference proceedings and clinical trial registers. The main end-point was OS. Investigators were contacted to obtain the individual patient data, which was recorded, harmonised and checked. A random-effects Cox model, stratified by trial, was used for meta-analysis and subgroup analyses were preplanned. Results: 16 trials were identified as eligible. Individual patient data were obtained from 12 trial and 2478 patients. CS was associated with an improved OS versus surgery, hazard ratio (HR) = 0.83 [0.72–0.96], p < 0.0001, translating to an absolute benefit of 5.7% at 5-years from 16.8% to 22.5%. Treatment effects did not vary substantially between adenocarcinoma (HR = 0.73 [0.62–0.87]) and squamous cell carcinoma (HR = 0.91 [0.76–1.08], interaction p = 0.26). A somewhat more pronounced effect was observed in gastro-oesophageal junction (HR = 0.68 [0.50–0.93]) versus TE (HR = 0.87 [0.75–1.00], interaction p = 0.07). CS was also associated with a greater disease-free survival (HR = 0.74 [0.64–0.85], p < 0.001). Conclusions: Neoadjuvant chemotherapy conferred a better OS than surgery alone and should be considered in all anatomical location and histological subtypes.

Network meta-analysis (NMA) allows the combination of direct and indirect evidence from a set of randomized clinical trials. Performing NMA using individual patient data (IPD) is considered as a "gold standard" approach as it provides several advantages over NMA based on aggregate data. For example, it allows to perform advanced modeling of covariates or covariate-treatment interactions. An important issue in IPD NMA is the selection of influential parameters among terms that account for inconsistency, covariates, covariate-by-treatment interactions or nonproportionality of treatments effect for time to event data. This issue has not been deeply studied in the literature yet and in particular not for time-to-event data. A major difficulty is to jointly account for between-trial heterogeneity which could have a major influence on the selection process. The use of penalized generalized mixed effect model is a solution, but existing implementations have several shortcomings and an important computational cost that precludes their use for complex IPD NMA. In this article, we propose a penalized Poisson regression model to perform IPD NMA of time-to-event data. It is based only on fixed effect parameters which improve its computational cost over the use of random effects. It could be easily implemented using existing penalized regression package. Computer code is shared for implementation. The methods were applied on simulated data to illustrate the importance to take into account between trial heterogeneity during the selection procedure. Finally, it was applied to an IPD NMA of overall survival of chemotherapy and radiotherapy in nasopharyngeal carcinoma.

In a rat model of metabolic syndrome (MS), our previous studies have shown that dietary sodium restriction prevents both metabolic and cardiac damages associated with MS. Our aim is now to investigate whether the beneficial effects of sodium restriction could be mediated by endothelial to mesenchymal (EndoMT) transition in the myocardium thereby preventing cardiac fibrosis.High fructose (60%) Sprague Dawley rats were divided into 2 groups: low sodium (in vitro model of EndoMT, using primary human aortic endothelial (HAoE) cells that were transdifferentiated with TGF-β2 (10ng/ml). We evidenced in HAoE cells the co-expression of Pecam-1 and collagen-1, as a signature of EndoMT. Especially, fibulin 5, one of the genes identified by transcriptomics was found upregulated (13 folds) in the presence of TGF-β2, confirming its potential role in EndoMT. Our study shows that EndoMT is involved in the prevention of cardiac fibrosis by sodium restriction in our rat model of MS. We also confirmed the involvement of ew genes that could be of interest to improve the management of cardiac fibrosis.

Imprinting is an early sensory life experience that induces adult behaviours, such as mother recognition or homing. In a previous study, we demonstrated a striking olfactory imprinting in C. elegans that can be inherited over generations. When exposed to specific odorants during a timely controlled post-hatch period, C. elegans worms display during adulthood an enhanced migration towards these molecules. In order to unveil some of the genetic and epigenetic factors that are responsible for such a behavioural plasticity, we assessed the role of heterochronic genes using a candidate gene approach. We report here that translation of the Hunchback-Like 1 (HBL1) transcription factor in the sensory processing interneuron AIY, is a determining factor for olfactory plasticity timing in C.elegans. HBL1 may associate to the SPR1/CoREST co-repressor, the lysine demethylase SPR5/LSD1 and the histone deacetylase HDA3 to lengthen the plasticity period, whereas the translation initiation factor IFE-4 and the histone deacetylase HDA2 abridge it. We also observed that lengthened plasticity periods allow proportionally faster stable behavioral adaptation of C. elegans populations. We conclude that plasticity timing is a key factor, not only to transiently adapt individuals but also to stably adapt animal populations via multigenerational accumulation of experience.

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation.. .) and patient-related factors (comorbidities, sequelae of previous irradiation.. .), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques., Malgré les progrès dans la prise en charge des carcinomes épidermoïdes des voies aérodigestives supé-rieures (VADS), de nombreux patients vont développer une récidive en territoire irradié ou un second primitif. Devant la très grande hétérogénéité de ces patients, des facteurs liés à la maladie (localisa-tion, volume, récidive ou second primitif, intervalle depuis la première irradiation, etc.), des facteurs liés au patient (comorbidités, séquelles de la première irradiation.. .), les indications sont posées au cas par cas. Les données historiques de réirradiation, bien que rapportant des données d'efficacité parfois encourageantes, font état de taux de toxicité de grades 4 et 5 importants. Avec la généralisation récente des techniques de radiothérapie plus précises et mieux conformées comme la radiothérapie confor-mationnelle avec modulation d'intensité (RCMI) ou la radiothérapie stéréotaxique (SBRT), le rapport bénéfice/risque de la réirradiation a évolué ces dernières années. L'objectif de cette revue est de faire le point sur les réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures en termes de sélection de patients, et de techniques modernes de radiothérapie. © 2019 Société franç aise de radiothérapie oncologique (SFRO).

The risk of lymph node invasion, in case of prostate cancer, increases with the clinical stage of the disease, the Gleason score of prostate biopsies and the value of PSA at diagnosis. Historically, beyond 15% risk of lymph node involvement, irradiation of the pelvic areas was performed with prostate radiotherapy (RT) to take into account the risk of occult lymph node metastasis in patients at risk, but the benefit of this therapeutic approach remains to be demonstrated. The data from surgical lymph node dissection seem to question the risk levels, the escalation of the dose on the prostate increases the survival without relapse, the contribution of image-guided radiotherapy, (IGRT) and modulation of intensity (IMRT), decreases the toxicity of pelvic RT. This article reviews the principles of prophylactic ganglion irradiation for prostate cancer and discusses its relevance, current uncertainties, and prospective trials.

Post-therapeutic follow-up of patients with head and neck cancer involves numerous professionals. The radiation oncologist should play an active role in this process. His oncological knowledge and technical expertise position him as a cornerstone for the detection of recurrences from the treated tumor, the research of second primary cancers and the screening of potential side-effects induced by the different treatments administered. To improve the benefits/costs ratio and allow good patient-compliance, follow-up programs should be built through close collaboration between the different contributors and planned according to a feasible schedule. Paraclinical exams must be arranged to respond to accurate objectives. Patient-education is essential to ensure the patient's full understanding and active participation. Finally, the transfer of the long-term follow-up of cancer survivors from specialists to primary care physicians is relevant but would require a prospective evaluation of its efficiency for this specific population.

National audience; Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.

Ultrasound imaging of the testis represents the standard-of-care initial imaging for the diagnosis of TGCT, whereas computed tomography (CT) plays an integral role in the initial accurate disease staging (organ-confined, regional lymph nodes, or sites of distant metastases), in monitoring the response to therapy in patients who initially present with non-confined disease, in planning surgical approaches for residual masses, in conducting follow-up surveillance and in determining the extent of recurrence in patients who relapse after treatment completion. CT imaging has also an important place in diagnosing complications of treatments. The aims of this article are to review these different roles of CT in primary TGCT and focus on different pitfalls that radiologists need to be aware of.

TPS12142 Background: Despite improvements in irradiation techniques, pelvic radiotherapy is responsible for acute and late adverse events in the bladder, defined as radiation cystitis (CysR). The early symptoms of bladder lesions secondary to pelvic irradiation are likely to occur during treatment or after radiotherapy in approximately 50% of irradiated patients. Acute radiation-related injuries are the first step of the fibrosis process. Fibrosis causes loss of bladder function and has a significant impact on the quality of life of the patients.The pathophysiology of CysR is not well understood, in particular because of the risks of complications caused by accessing the bladder tissue after irradiation, thereby limiting our ability to investigate this process and develop treatments. The main objective of our study is to assess the correlation of biologic biomarkers with the intensity of acute CysR and the quality of life of patients, evaluated with the digital telemonitoring platform Cureety. Methods: Patients with intermediate-risk localized prostate cancer and eligible for localized radiotherapy will be included. Inflammatory biomarkers will be analyzed on urine and blood samples before the initiation of radiotherapy, at week 4, 12 and 48 of irradiation, by quantitative methods such as the Multiplex Luminex assay, cytometry in flow and enzyme-linked immunosorbent assay ELISA. We will also characterize the gut and urinary microbiota in stool and urine samples using 16S rRNA sequencing technology. This is in order to assess the impact of the fecal and urinary microbiota in acute CysR. Between sample collection visits, patients will answer various questionnaires relating to the symptoms of radiation cystitis (IPSS), adverse events and quality of life (FACT-P), using the digital telemonitoring platform Cureety. Upon receipt of the questionnaires, an artificial intelligence algorithm will process the information and classify the patients according to the severity of symptoms and adverse reactions reported in accordance with CTCAE / IPSS. This will ultimately allow us to correlate urinary, blood and fecal biomarker levels with the severity of acute CysR symptoms and the quality of life reported by the patients. Conclusion: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute CysR. In addition, the 1-year post-treatment follow-up will allow us to predict which patients are at risk for late CysR and to stratify these patients towards radioprotective treatment. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the quality of life of patients. Clinical trial information: 2021A0319635.

Resume Objectif de l’etude Pour faciliter la formation a la delineation, la Societe francaise de radiotherapie oncologique (SFRO) et l’association de formation continue en oncologie radiotherapie (Afcor) ont cree en 2008 un site Internet de radioanatomie et d’aide a la delineation. Materiel et methodes Entre 2015 et 2017, une mise a jour du site a ete entreprise, necessitant la mise en place de deux parties : des cours theoriques d’une part, et des ateliers de delineation en ligne d’autre part. Resultats Un nouveau site exploitant l’ensemble des nouvelles technologies numeriques a ete mis en ligne. Les cours ont ete realises sous forme de videos commentees et consultables a tout moment. La partie pratique offre une interface de delineation en ligne qui genere a la fin de l’exercice un rapport permettant de quantifier la qualite de sa delineation. Conclusion Siriade 2.0 est un outil numerique innovant qui s’inscrit en complement des formations initiales et continues deja disponibles.

Purpose: Lip carcinoma represents one of the most common types of head and neck cancer. Brachytherapy is a highly effective therapeutic option for all stages of lip cancers. We report our experience of pulsed dose rate brachytherapy (PDR) as treatment of lip carcinoma. Methods and Materials: this retrospective single center study included all consecutive patients treated for a lip PDR brachytherapy in our institution from 2010 to 2019. The toxicities and outcomes of the patients were reported, and a retrospective quality of life assessment was conducted by phone interviews (FACT H&amp, N). Results: From October 2010 to December 2019, 38 patients were treated in our institution for a lip carcinoma by PDR brachytherapy. The median age was 73, and the majority of patients presented T1-T2 tumors (79%). The median total dose was 70.14 Gy (range: 60–85 Gy). With a mean follow-up of 35.4 months, two patients (5.6%) presented local failure, and seven patients (19%) had lymph node progression. The Kaplan–Meier estimated probability of local failure was 7.2% (95% CI: 0.84–1) at two and four years. All patients encountered radiomucitis grade II or higher. The rate of late toxicities was low: three patients (8.3%) had grade II fibrosis, and one patient had grade II chronic pain. All patients would highly recommend the treatment. The median FACT H&amp, N total score was 127 out of 148, and the median FACT H&amp, N Trial Outcome Index was 84. Conclusions: This study confirms that an excellent local control rate is achieved with PDR brachytherapy as treatment of lip carcinoma, with very limited late side effects and satisfactory functional outcomes. A multimodal approach should help to improve regional control.

Background The prognostic significance of nodal involvement is not well established in head and neck mucosal melanoma (HNMM). Methods A retrospective, monocentric study was performed on 96 patients with HNMM treated between 2000 and 2017. Results At diagnosis, seventeen patients (17.8%) were cN1, with a higher risk for HNMM arising from the oral cavity (p = 0.01). cN status had no prognostic value in patients with nonmetastatic resectable HNMM. No occult nodal metastasis was observed in the cN0 patients after a nodal dissection (ND). The nodal recurrence rate was similar in the cN1 and the cN0 patients. No isolated nodal recurrences were noted. Among the patients who underwent a ND, no benefit of this procedure was noted. Conclusions cN1 status is not a prognostic factor in patients with resectable HNMM. Elective ND should not be systematically performed in cN0 HNMM.

ATR checkpoint signalling is crucial for cellular responses to DNA replication impediments. Using an optogenetic platform, we show that TopBP1, the main activator of ATR, self-assembles extensively to yield micron-sized condensates. These opto-TopBP1 condensates are functional entities organized in tightly packed clusters of spherical nano-particles. TopBP1 condensates are reversible, occasionally fuse and co-localise with TopBP1 partner proteins. We provide evidence that TopBP1 condensation is a molecular switch that amplifies ATR activity to phosphorylate checkpoint kinase 1 (Chk1) and slowdown replication forks. Single amino acid substitutions of key residues in the intrinsically disordered ATR-activation domain disrupt TopBP1 condensation and, consequently, ATR/Chk1 signalling. In physiologic salt concentration and pH, purified TopBP1 undergoes liquid-liquid phase separation in vitro. We propose that the actuation mechanism of ATR signalling is the assembly of TopBP1 condensates driven by highly regulated multivalent and cooperative interactions.

Introduction et but de l’etude La question ethique est une thematique emergente et peu exploree dans le monde de la radiotherapie. L’objectif de notre travail etait de preciser le questionnement ethique en radiotherapie dans une approche multiprofessionnelle. Materiel et methodes Une etude multicentrique a ete realisee dans 22 departements de radiotherapie francais, a partir d’un questionnaire Google Form (dix questions) soumis aux oncologues radiotherapeutes, manipulateurs d’electroradiologie, physiciens medicaux, assistantes medicales et cadres. Le questionnaire visait a mieux comprendre la frequence et la nature du questionnement ethique dans les departements de radiotherapie, ainsi que le besoin de formation. Resultats et analyse statistique Un total de 200 personnes a repondu aux questionnaires, se repartissant en : oncologues radiotherapeutes (37 %), manipulateurs d’electroradiologie (37 %), physiciens medicaux (12,5 %), assistantes medicales (10 %) et cadres (3,5 %). Le nombre moyen d’annees d’experience en radiotherapie etait de 12 ans (extremes : 6 mois - 40 ans). En termes de frequence dans la pratique de radiotherapie, la question ethique se posait : frequemment (plus d’une fois par mois ; 52,5 %), rarement (entre trois et dix fois par an ; 35,5 %), exceptionnellement (moins de deux fois par an ; 9,5 %) et jamais (2,5 %). En termes de nature, la question ethique concernait : la comprehension et/ou l’acceptation du traitement par les patients (71 %), les objectifs attendus du traitement (65 %), la lourdeur technique et organisationnelle du traitement (62 %) et le cout du traitement (13 %). Une specificite de la question ethique en radiotherapie etait reconnue pour 64 % des personnels. Les questions ethiques etaient effectivement discutees dans les departements de radiotherapie : jamais (18,5 %), parfois (47,5 %), souvent (10,5 %) et ne se prononce pas (18,5 %). Les questions d’ethique etaient considerees comme suffisamment discutees dans ces departements : non (47,5 %), oui (14 %) et ne se prononce pas (38,5 %). Seuls 17 % des personnels ont deja eu une formation en ethique medicale. Le besoin de formation specifique etait ressenti par 83,5 % des personnels n’ayant jamais eu de formation. Conclusion La question ethique se pose effectivement assez frequemment et specifiquement en radiotherapie, avec un sentiment d’insuffisance a la fois de discussion dans les departements et de formation. Les questions principales d’ethique concernent la comprehension du traitement par les patients, ses objectifs et la lourdeur de ceux-ci.

Introduction Individual patient data (IPD) present particular advantages in network meta-analysis (NMA) because interactions may lead an aggregated data (AD)-based model to wrong a treatment effect (TE) estimation. However, fewer works have been conducted for IPD with time-to-event contrary to binary outcomes. We aimed to develop a general frequentist one-step model for evaluating TE in the presence of interaction in a three-node NMA for time-to-event data. Methods One-step, frequentist, IPD-based Cox and Poisson generalized linear mixed models were proposed. We simulated a three-node network with or without a closed loop with (1) no interaction, (2) covariate-treatment interaction, and (3) covariate distribution heterogeneity and covariate-treatment interaction. These models were applied to the NMA (Meta-analyses of Chemotherapy in Head and Neck Cancer [MACH-NC] and Radiotherapy in Carcinomas of Head and Neck [MARCH]), which compared the addition of chemotherapy or modified radiotherapy (mRT) to loco-regional treatment with two direct comparisons. AD-based (contrast and meta-regression) models were used as reference. Results In the simulated study, no IPD models failed to converge. IPD-based models performed well in all scenarios and configurations with small bias. There were few variations across different scenarios. In contrast, AD-based models performed well when there were no interactions, but demonstrated some bias when interaction existed and a larger one when the modifier was not distributed evenly. While meta-regression performed better than contrast-based only, it demonstrated a large variability in estimated TE. In the real data example, Cox and Poisson IPD-based models gave similar estimations of the model parameters. Interaction decomposition permitted by IPD explained the ecological bias observed in the meta-regression. Conclusion The proposed general one-step frequentist Cox and Poisson models had small bias in the evaluation of a three-node network with interactions. They performed as well or better than AD-based models and should also be undertaken whenever possible.

Background and purposeThe Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.Materials and methodsPublished or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT+CT or adding another timing of CT to LRT+CT (main question), or comparing induction CT+radiotherapy to radiotherapy+concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.ResultsFor the main question, 101 trials (18951 patients, median follow-up of 6.5years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p&nbsp

Contains fulltext : 235407.pdf (Publisher’s version ) (Closed access) BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRT(P)) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRT(P) (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (IC(TaxPF)-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and IC(TaxPF) followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or IC(TaxPF)-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Resume La curietherapie, par son mode d’action, comme par ses resultats cliniques de haut niveau de preuve, represente une technique d’irradiation des cancers specifique dans la prise en charge des cancers comme de certaines rechutes en territoire irradie. Apres la periode faste des annees 1980–1990, la curietherapie a progressivement perdu de son attrait. Afin d’apporter une solution concrete a cette situation deletere, il est important que les tutelles, les organismes payeurs, les associations de patients, les specialistes d’organes et les oncologues radiotherapeutes comprennent les raisons qui ont conduit a une telle situation ainsi que les risques encourus. Un enseignement juge insuffisant, une valorisation inadaptee et une image vieillissante de la curietherapie constituent les trois raisons essentielles de cette degradation et representent les trois enjeux majeurs conditionnant son maintien dans l’arsenal therapeutique anticancereux. Une communication, adaptee au sein de la communaute des oncologues radiotherapeutes, comme avec les autres societes savantes, est primordiale de meme qu’aupres des tutelles et des associations de patients. Il est capital que la curietherapie soit (re)connue afin de lui rendre tout son interet pour les patients qui pourront en beneficier.

Paraspeckles are nuclear membraneless structures composed of a long non-coding RNA, Nuclear-Enriched-Abundant-Transcript-1 and RNA binding proteins, which associate numerous mRNAs. It is therefore believed that their cellular function is to sequester in the nucleus their associated proteins and/or target mRNAs. However, little is known about the molecular determinant in mRNA targets that allow their association to paraspeckles except that inverted repeats of Alu sequences (IRAlu) present in 3’UTR of mRNAs may allow this association. While in a previous study we established the list of paraspeckle target RNAs in a rat pituitary cell line, we didn’t find however, inverted repeated SINEs, the rat equivalent of primate IRAlus in 3’UTR of these RNAs. By developing a candidate gene strategy, we selected a paraspeckle target gene, namely calreticulin mRNA, and we searched for other potential RNA recruitment elements in its 3’UTR, since 3’UTRs usually contain the sequence recognition for nuclear localization. We found a 15-nucleotide sequence, present as a tandem repeat in 3’UTR of this mRNA, which is involved in the nuclear retention by paraspeckles. While being not overrepresented in the 3’UTR of the paraspeckle target RNAs, this recruitment element was present in near 30% of all 3’UTR mRNAs. In addition, since an oligonucleotide containing this sequence binds the paraspeckle protein component HNRNPK, it is proposed that HNRNPK may constitute a bridging protein between paraspeckles and target mRNAs.

Purpose: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial. Methods and Materials: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients

Nearly one-third of the patients who undergo prostatectomy for prostate cancer have a biochemical recurrence (BCR) during follow-up. While several randomized trials have shown that adjuvant radiation therapy (aRT) improves biochemical control, this strategy has not been widely used because of the risk of toxicity and the fear of overtreating patients who would not have relapsed. In addition, the possibility of close PSA monitoring in the era of ultrasensitive assays enables to anticipate early salvage strategies (sRT). Three recent randomized trials and their meta-analysis have confirmed that aRT does not improve event-free survival compared to sRT, imposing the latter as the new standard of treatment. The addition of androgen deprivation therapy (ADT) to RT has been shown to improve biochemical control and metastasis-free survival, but the precise definition of to whom it should be proposed is still a matter of debate. The development of genomic tests or the use of artificial intelligence will allow more individualized treatment in the future. Therapeutic intensification with the combination of new-generation hormone therapy and RT is under study. Finally, the growing importance of metabolic imaging (PET/CT) due to its performance especially for low PSA levels will help in further personalizing management strategies.

BackgroundProstate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant PC (CRPC). We investigated a mouse model of PC as well as specimens from PC patients to unravel an unsuspected contribution of thymus-derived T lymphocytes and the intestinal microbiota in the efficacy of ADT.MethodsPreclinical experiments were performed in PC-bearing mice, immunocompetent or immunodeficient. In parallel, we prospectively included 65 HSPC and CRPC patients (Oncobiotic trial) to analyze their feces and blood specimens.ResultsIn PC-bearing mice, ADT increased thymic cellularity and output. PC implanted in T lymphocyte-depleted or athymic mice responded less efficiently to ADT than in immunocompetent mice. Moreover, depletion of the intestinal microbiota by oral antibiotics reduced the efficacy of ADT. PC reduced the relative abundance of Akkermansia muciniphila in the gut, and this effect was reversed by ADT. Moreover, cohousing of PC-bearing mice with tumor-free mice or oral gavage with Akkermansia improved the efficacy of ADT. This appears to be applicable to PC patients because long-term ADT resulted in an increase of thymic output, as demonstrated by an increase in circulating recent thymic emigrant cells (sjTRECs). Moreover, as compared with HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs. While feces from healthy volunteers restored ADT efficacy, feces from PC patients failed to do so.ConclusionsThese findings suggest the potential clinical utility of reversing intestinal dysbiosis and repairing acquired immune defects in PC patients.

Head and neck cancer survival rates are increasing as a result of more advanced treatment regimens [1–7]. The increasing number of head and neck cancer survivors stresses the importance of preventing late radiation-induced toxicities, which may persist or occur years after treatment, gravely impacting the quality of life [8]. Owing to the intrinsic properties of particles, proton therapy has the ability to deliver dose more conformal to the tumor, consequently sparing more normal tissue surrounding it [9–11]. While proton therapy arguably can be beneficial for a large proportion of head and neck cancer patients, it is currently still limited in availability and there is a benefit gradient with regard to the estimated toxicities [12, 13]. Introduced by Langendijk et al [14], the model-based approach is a systematic way to identify patients that may benefit most from proton therapy based on the predicted toxicity risk, that is, normal tissue complication probability (NTCP). In other words, NTCP can be considered the individual percentile risk for a patient to develop a certain radiation-associated toxicity (eg, risk of 40% to develop feeding tube dependence). NTCP-guided treatment decision support requires reliable NTCP models, which generally embody the toxicity's association with organ-at-risk (OAR)-specific dose-volume histogram parameters. The development of (semi)auto-contouring of head and neck OARs has facilitated more time-efficient and robust extraction of dose-volume histogram information, particularly from OARs that are not contoured for clinical planning purposes [15–18]. In addition, clinical factors (eg, chemotherapy, smoking status, age, xerostomia before radiotherapy) can contribute to or interact with the effect of radiation dose in developing radiation-induced toxicities [15–17, 19–21]. The aims of this systematic review were (1) to describe how NTCP models are developed and validated, (2) to perform and present a systematic review of existing NTCP models for photon or proton therapy for head and neck cancers, and (3) to explore and propose future directions, concerning novel NTCP model types, as well as methodologic development. Normal Tissue Complication Probability Model Development and Validation NTCP models are classifiers, meaning they aim to stratify between patients at high risk and low risk for developing a toxicity. In contrast to the historically used Lyman–Kutcher–Burman NTCP models [18, 22, 23], which are only based on a single-dose variable, multivariable logistic regression represents the current modeling preference as shown in the following equation: where s = β0 + β1·variable1 + β2·variable2… + βn·variablen. The β0 is the intercept coefficient, which is a constant; the other β are the coefficients multiplied by, thus linked to, a specific variable, which could be for example the mean contralateral parotid gland dose or baseline xerostomia complaints. Model development is performed by “training” on training data to (1) select an optimal set of variables that are significantly associated with the predicted toxicity, and (2) estimate the model coefficients (β) to fit the model to the data. Figure 1 illustrates a hypothetical example of an NTCP classification (ie, the equation); with a so-called loss function, the most optimal distinction is sought to separate patients with and without a toxicity. The linear prediction (s in the equation) that is obtained from this optimization process is the basis of the resulting logistic regression NTCP model (visual representation in Figure 1). Open in a separate window Figure 1. Normal tissue complication probability model optimization.

International audience; The management of early metastatic prostate cancer is based on systemic treatment by androgen deprivation therapy with or without chemotherapy or next-generation anti-androgen therapies. Local treatment of the prostate was initially used only to alleviate local symptoms. However, local radiotherapy of the prostate has been the subject of retrospective and prospective studies in patients with better prognostic factors, particularly in oligometastatic status. The results of these studies support that prostate radiotherapy can prolong the survival of patients with a low metastatic burden. This article states the biological bases, the main published and future published studies aimed to embed this strategy to optimize therapeutic management.

International guidelines recommend specific interventions to reduce cancer-related fatigue (CRF). Evidence suggests underutilization of these interventions among breast cancer survivors. The QualFatigue study aimed to explore the potential factors influencing the use of specific interventions, for relief, in patients with CRF through qualitative analyses.Patients with stage I-III breast cancer, and CRF ≥4 on a 10-point numerical scale were recruited within 6-24 months at the end of their primary treatment. Semi-structured interviews were performed. Emergent themes were identified using a stepped content analysis (QDA Miner software).Data saturation was achieved with 15 interviews. Four main themes emerged as potential sources of influence in the participants' use of specific interventions: (1) expectations regarding the management of CRF, (2) representations of the benefits provided by the interventions, (3) individual physical and psychological conditions, and (4) social and environmental situations. Six key levers came out transversally to optimize the use of specific interventions to relieve CRF: (1) listening and recognition of the individual difficulties and needs; (2) individual and global health assessments; (3) information and advice on how to manage CRF; (4) discussion groups focused on the management of CRF; (5) group activities; and (6) professional and personalized guidance.This study calls for multi-level action to address many persistent barriers and exploit levers in the management of CRF.

In this article we review some machine learning methods for the design of nanomaterials. The first part will discuss how to use neural network to build a predictive model of the optical properties of a certain material or structure. The second part is dedicated to the optimization and reverse engineering of an optical material using generative networks.

Evaluating the log-sum-exp function or the softmax function is a key step in many modern data science algorithms, notably in inference and classification. Because of the exponentials that these functions contain, the evaluation is prone to overflow and underflow, especially in low-precision arithmetic. Software implementations commonly use alternative formulas that avoid overflow and reduce the chance of harmful underflow, employing a shift or another rewriting. Although mathematically equivalent, these variants behave differently in floating-point arithmetic and shifting can introduce subtractive cancellation. We give rounding error analyses of different evaluation algorithms and interpret the error bounds using condition numbers for the functions. We conclude, based on the analysis and numerical experiments, that the shifted formulas are of similar accuracy to the unshifted ones, so can safely be used, but that a division-free variant of softmax can suffer from loss of accuracy.

International audience; Computing units that carry out a fused multiply-add (FMA) operation with matrix arguments, referred to as tensor units by some vendors, have great potential for use in scientific computing. However, these units are inherently mixed precision and existing rounding error analyses do not support them. We consider a mixed precision block FMA that generalizes both the usual scalar FMA and existing tensor units. We describe how to exploit such a block FMA in the numerical linear algebra kernels of matrix multiplication and LU factorization and give detailed rounding error analyses of both kernels. An important application is to GMRES-based iterative refinement with block FMAs, for which our analysis provides new insight. Our framework is applicable to the tensor core units in the NVIDIA Volta and Turing GPUs. For these we compare matrix multiplication and LU factorization with TC16 and TC32 forms of FMA, which differ in the precision used for the output of the tensor cores. Our experiments on an NVDIA V100 GPU confirm the predictions of the analysis that the TC32 variant is much more accurate than the TC16 one, and they show that the accuracy boost is obtained with almost no performance loss.

In this Letter, we demonstrate how harmonic oscillator equations can be integrated in a neural network to improve the spectral response prediction for an optical system. We use the optical properties of a one-dimensional nanoslit array for a practical implementation of the study. This method allows to build more generalizable relations between the input parameters of the array and its optical properties, showing a 20-fold improvement for parameters outside the range used for the training. We also show how this model generates the output spectrum from phenomenological relationships between the input parameters and the output spectrum, indicating how it grasps the physical mechanisms of the optical response of the structure. (C) 2020 Optical Society of America

Background and purpose To identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10–15 year) freedom from prostate cancer. Materials and methods Data from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10–15 years. Results For the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3–99.0) at 10 years and 96.1% (95% CI 94.8–97.2) at 15 years. Three independent validation cohorts confirmed 97–99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p Conclusions Since 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years’ follow-up after LDR brachytherapy.

To determine outcomes and toxicities after reirradiation for locally recurrent nasopharyngeal carcinoma (rNPC) and to apply a prognostic index in a non-endemic region. We retrospectively reported progression-free survival (PFS), overall survival (OS), and treatment-related toxicities in patients treated with curative intent for locally rNPC. We applied the prognostic model for OS and grade 5 radiotherapy (RT)-related toxicities published by Li et al. and evaluated its prognostic accuracy by receiver operating characteristic (ROC) curve analysis. Between 2005 and 2018, 33 patients were treated for rNPC in our institution. Median follow-up was 60 months. The mean time to local recurrence was 75 months. Six (18%) patients had a persistent grade 3 toxicity from a previous RT course. The median re-RT dose was 66 Gy. After re-RT, 13 patients had local failure and 3 patients had metastatic recurrence. Median PFS was 18 months with a 5-year PFS rate of 29%. Median OS was 35 months with a 5-year OS rate of 37%. Grade 3 or higher toxicities rate was 74%. There were 21% grade 5 toxicities. The median time to a grade 5 toxicity was less than 6 months following re-RT. The prognostic nomogram was not predictive for OS or grade 5 toxicities. Reirradiation of rNPC is an effective treatment but is associated with a high rate of life-threatening toxicity. Stratification of patients based on their risk of developing severe toxicity is needed to select patients who will most likely benefit from re-RT.

We investigated the prognostic factor of N3 head and neck squamous cell carcinoma (HNSCC), including the role of upfront neck dissection (UFND) before radiotherapy (RT).We retrospectively reviewed the charts of consecutive N3 HNSCC patients treated with curative intent RT.In the study, 323 N3 HNSCC patients were included. Of those, 125 patients (39%) had UFND. Median follow-up was 3.9 years (0-14.8 years). Overall survival (OS) at 5 years was 31.2%, and progression-free survival (PFS) was 26%. In the multivariate analysis, OS was improved in PS 0, T1-2 tumors, patients receiving concurrent chemotherapy, never or former smokers, and UFND. UFND was strongly associated with increased OS (45.7% vs. 21.2%, P .001), and PFS (P .001). Regardless of neck node size, UFND improved survival (P = .001 for ≤ 7 cm and P = .004 for 7 cm).UFND could improve treatment outcomes in N3 HNSCC, especially for non-oropharyngeal cancer, regardless of neck node size.2B Laryngoscope, 131:E844-E850, 2021.

Introduction Neoadjuvant chemotherapy with docetaxel and estramustine (DE) significantly improved relapse-free survival in patients with high-risk localized prostate cancer treated with androgen deprivation therapy (ADT) for 3 years and a local treatment in the GETUG-12 phase III trial. We sought to explore whether the addition of DE impacts long-term treatment-related side effects. Patients and Methods Patients randomized within the UNICANCER GETUG-12 trial at Gustave Roussy who were alive when ADT was discontinued were followed-up prospectively. Serum testosterone levels and clinical data regarding body weight, libido, erection, and cardio-vascular events were collected. Results Seventy-eight patients were included: 36 patients had been treated with ADT plus a local treatment and 42 with ADT+DE plus a local treatment. With a median follow-up of 5.9 years after ADT discontinuation, serum testosterone levels returned to normal values (> 200 ng/mL) for 57 (78%) of 72 evaluable patients, and 29 (43%) of 68 evaluable patients reported erections allowing intercourse without medical assistance. No impact of DE on testosterone level recovery, libido, quality of erections, and changes in body weight after ADT discontinuation was detected. The incidence of cardiovascular events was low and similar in both treatment arms. Conclusion Treatment with DE was not associated with excess long-term castration-related toxicity in men with high-risk localized prostate cancer. The relapse-free survival improvement seen with DE in GETUG-12 is likely not related to differed testosterone recovery.

Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers. The diagnostic confirmation, if needed, requires an urgent biopsy reread by an expert pathologist with additional immunohistochemical and molecular analyses. Therapeutic management, defined in multidisciplinary meetings, respecting the patient’s choice, must start within days following diagnosis. For localized disease diagnosed after primary surgical treatment, adjuvant chemo-radiotherapy is recommended. In the event of locally advanced or metastatic disease, the prognosis is very poor. Treatment should then involve chemotherapy or targeted therapy and decompressive cervical radiotherapy. Here we will review current knowledge on ATC and provide perspectives to improve the management of this deadly disease.