Background: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).Patients and methods: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20.Results: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade >3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash.Conclusion: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Anal squamous cell carcinoma (ASCC) is rare and 2/3 of patients (pts) are >65 years (y) at diagnosis. Standard of care for localized stages is chemoradiotherapy (CRT) but data about elderly are scarce in the literature. We aimed to describe characteristics, therapeutic management and outcomes of elderly pts and compare them to those of younger pts. We also determined prognostic factors in elderly with ASCC. All consecutive pts treated between 2015/01 and 2020/04 for a localized ASCC from the French multicenter ANABASE cohort were included. Two groups were defined according to age: elderly (≥75 y) and non-elderly (<75 y). Among 1378 pts included, 1015 were treated by radiotherapy or CRT: 202 (19.9%) and 813 (80.1%) in the elderly and non-elderly groups, respectively. In the elderly group, median age was 79 y [IQR: 77-84], the proportion of women was more important (p=0.0145) while there were less performance status (PS) 0-1 (p<0.001), smokers (p<0.001) and HIV-infected (p<0.001) pts than in the non-elderly group. Other baseline and tumoral characteristics were similar. Inguinal irradiation and concomitant chemotherapy were also less frequently performed (p=0.04 and p<0.001). Median follow-up was 35.5 months. In the elderly group, 3-year overall survival (OS), recurrence-free survival (RFS) and colostomy-free survival (CFS) were 82.9% (75.6-88.2), 72.4% (64.7-78.8) and 78.0% (70.5-83.9), respectively. Complete response rate at 4-6 months of treatment was 70.3%. There was no significant difference for all outcomes and in toxicity patterns between groups. In multivariate analyses for the elderly group, PS≥2 and locally advanced (T3-T4 or N+) tumors were associated with poor OS (HR=3.4 [1.4;8.3] and HR=2.80 [1.2;7.1]), RFS (HR=2.4 [1.2;4.9] and HR=3.1 [1.5;6.4]) and CFS (HR=3.8 [1.8;8.1] and HR=3.0 [1.4;6.7]), and treatment interruption was associated with poor RFS (HR=1.9 [1.1;3.5]). In ANABASE cohort, age does not influence tumor and tolerance outcomes of localized ASCC. The optimal curative treatment should be offered to elderly pts after oncogeriatric assessment.

Based on the hypothesis of a potential synergistic effect of the anti-PD1 pembrolizumab when combined with RT, this new combination was tested in a randomized trial against the well-established standard of care (SOC) cetuximab-RT in LA-HNSCC. In this phase II randomized trial, patients with non operated stage III-IVa-b SCC of oral cavity, oropharynx, hypopharynx and larynx and unfit for receiving high dose of cisplatin were enrolled. Patients received once-daily IMRT up to 69,96 Gy concomitant with cetuximab (Cetux-RT arm: 400 mg/m2 loading dose and 250 mg/m2 weekly) or pembrolizumab (Pembro-RT arm: 200 mg Q3W during RT). The primary endpoint was 15-month Loco-Regional Control (LRC) rate and secondary endpoints included Progression-free survival (PFS), Overall Survival (OS) and tolerance. To detect a difference between arms of 60% to 80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at 2-sided significance level of 0.20. Between May 2016 and October 2017, 131 patients were randomized and treated by 27 centers: 65 patients in Cetux-RT arm and 66 patients in Pembro-RT arm. The median age was 65 years, 92% were smokers, 60% of oropharynx (46% p16+), 41% of N2c-N3 with 25%, 56% and 19% of stage III, IVa and IVb respectively. Median follow-up was 25 months in both arms. Acute toxicity was lower in Pembro-RT arm than Cetux-RT arm: 74% vs 92% patients with at least one grade ≥ 3 acute adverse events (p=0.006), mainly due to dermatitis in radiation field, mucositis and cutaneous rash. LRC at 15 months were 59% in Cetux-RT arm and 60% in Pembro-RT arm, not significantly different: OR=1.05 (95%CI: 0.43-2.59, p=0.91). 2-year PFS rate was 40% in the Cetux-RT arm vs 42% in the Pembro-RT arm. There was no significant difference between arms for PFS: HR=0.83 (95%CI 0.53-1.29, p=0.41). 2-year OS rate was 55% in the Cetux-RT arm vs 62% in the Pembro-RT arm. OS was not significantly different between arms: HR=0.83 (95%CI: 0.49-1.40, p=0.49). Compared to the SOC cetuximab-RT, the anti-PD1 pembrolizumab concomitant with RT did not improve carcinologic outcomes but appeared less toxic.

In 2008, cobalt-60 contamination was discovered in parcels containing lift buttons from the French company MAFELEC, which is the supplier of the lift company OTIS. Inspections and investigations led by the French Nuclear Safety Authority (ASN) identified that this contamination was due to metal, which was imported from India. Consequently, ASN asked the French Institute of Radiation Protection and Nuclear Safety (IRSN) to evaluate the potential dosimetric impact of the contamination. Although the evaluated impact on workers of both companies and on the public was very low, this event had a significant impact in the media in France. Moreover, as MAFELEC supplies OTIS company all around the world, it turned out that contaminated lift buttons may have been sent abroad. In this context, the European ALARA Network (EAN), bringing together radiation protection organisations from 20 different European countries, which are sharing the objective of promoting the exchange and dissemination of information on practical experiences of the implementation of optimisation, has launched through its Forum a request on the management of this event in different countries in Europe. This article aims to summarize the information received from 13 different countries between January and July 2009.

With approximately 1500 cases per year in France, Hodgkin's lymphoma (HL) represents only 10 to 15 % of new cases of lymphomas, and 0.5 to 1 % of new cases of cancers. The management of this lymphoproliferative disease has undergone profound conceptual changes over time, allowing at present to obtain a cure rate of 75 to 80 % of all confused stage, and up to 90 % in case of early stage HL. If initial treatment consisted in an exclusive extensive (total or sub-total lymphoid) irradiation whatever the stage may be, the place of radiotherapy in the management of HL has evolved over time but remains today one of the cornerstones of the treatment. It becomes integrated within the framework of combined modality therapies associating chemotherapy then irradiation for the early stage HL, and stays a therapeutic alternative in all situations (in advanced stage and\or recurrent disease) which raises the issue of increasing the locoregional tumor control. Despite the undeniable contribution of radiotherapy in controlling the disease, delayed side effects of treatments are not negligible. So the long-term monitoring of treated patients is essential, mainly because of an increased risk of morbi-mortality due to cardiovascular events and/or secondary cancers. It is important to remember that even today the "Involved Field" irradiation type remains the gold standard, even if we witness at present the emergence of new types of irradiation, which aim to reduce the amount of irradiated tissues to try to limit the risks of delayed radio-induced complications. The purpose of this article is to clarify the specific aspects (epidemiological, radio-anatomical and prognostic characteristics) of HL, as well as the practical modalities of the irradiation (illustrated by a clinical case record) when an indication of radiotherapy is placed for its treatment.

Avec environ 10 000 nouveaux cas par an en France, les lymphomes malins non hodgkiniens représentent l’hémopathie maligne la plus fréquente et 5 à 10 % des nouveaux cas de cancer. Les lymphomes malins non hodgkiniens constituent un ensemble hétérogène de lymphopathies, regroupant des entités aux caractéristiques épidémiologiques, évolutives et pronostiques très différentes. Il existe plusieurs classifications des lymphomes malins non hodgkiniens mais sur le plan pratique, on individualise des lymphomes agressifs dont le lymphome B diffus à grandes cellules (qui est le lymphome le plus fréquent), et les lymphomes indolents dont le lymphome folliculaire et les lymphomes de MALT (Mucosa-associated lymphoid tissue). La place de la radiothérapie dans la prise en charge des lymphomes malins non hodgkiniens varie selon le sous-type précis de lymphome, mais elle est devenue de plus en plus limitée avec le temps. Généralement, elle ne trouve des indications à titre curatif que dans des situations de lymphomes malins non hodgkiniens localisés, soit associée à de la chimiothérapie dans le cadre d’un traitement combiné comme pour la prise en charge des lymphomes B diffus à grandes cellules, soit comme traitement exclusif, notamment dans les rares situations de lymphomes folliculaires localisés. Par ailleurs, les lymphocytes étant des cellules extrêmement radiosensibles, la radiothérapie conserve d’excellentes indications à but palliatif dans de volumineuses masses tumorales symptomatiques, et ce, quel que soit le sous-type de lymphome malin non hodgkinien. Il est important de rappeler qu’encore aujourd’hui l’irradiation de type « Involved Field » reste la technique de référence pour le traitement des lymphomes malins non hodgkiniens ganglionnaires, même si on assiste actuellement à l’émergence de nouveaux types d’irradiations visant à réduire les volumes irradiés pour tenter de limiter les risques de complications radio-induites tardives. L’objectif de cet article est de préciser les particularités (épidémiologiques, radio-anatomiques et pronostiques) des différents lymphomes malins non hodgkiniens (à l’exception des lymphomes cérébraux), ainsi que les modalités pratiques de l’irradiation (illustrées par des cas cliniques) lorsqu’une indication de radiothérapie est posée dans le cadre de leur prise en charge.

Fin 2008, une contamination au cobalt-60 a été découverte dans des colis contenant des boutons d’ascenseur de la société française MAFELEC, fournisseur de la compagnie d’ascenseurs OTIS. Les inspections et enquêtes menées par l’ASN (Autorité de sûreté nucléaire) ont permis d’identifier que cette contamination était due à du métal importé d’Inde. L’ASN a alors saisi l’IRSN (Institut de radioprotection et de sûreté nucléaire) pour évaluer les impacts dosimétriques potentiels de cette contamination. Bien que les impacts évalués pour les travailleurs des deux entreprises et pour le public soient très faibles, cet événement a eu un impact médiatique important en France. En outre, MAFELEC fournissant la société OTIS à travers le monde, des boutons contaminés avaient potentiellement été envoyés dans d’autres pays. Dans ce contexte, le réseau ALARA européen (EAN), regroupant des organismes et des institutions de radioprotection de 20 pays en Europe qui partagent l’objectif de favoriser l’échange et la diffusion d’informations sur les expériences pratiques en matière de mise en œuvre de la démarche d’optimisation, a lancé une requête via son Forum sur les moyens mis en œuvre pour gérer cet événement. Cet article présente la synthèse des informations concernant les 13 pays qui ont répondu à cette requête entre janvier et juillet 2009.

The 12th European ALARA Network (EAN) workshop on "ALARA issues arising for safety and security of radiation sources and security screening devices" took place in Vienna (Austria) in October 2009.The aim of that workshop was to consider how the implementation of ALARA 3 , in terms of planned and emergency situations, involving worker and public doses, is affected by the introduction of security-related measures.In the case of new equipment and procedures, there was also the question of whether exposures arising from security screening devices can be justified and optimised.This workshop consisted of invited oral presentations, which highlighted the main issues, and half of the programme was devoted to discussions within working groups on specific topics.During their discussions, the working groups identified recommendations dealing with the following topics: the implementation of the Code of Conduct and HASS 4 -ensuring ALARA; balancing security and safetyhow to achieve an optimum solution; the management of an emergency exposure situation from an ALARA perspective; the justification and optimisation of the use of security devices.The objective of this paper is to present the main conclusions and recommendations produced during the workshop.Individual presentations (papers and slides) as well as the reports from the working groups are available to download on the EAN website (http://www.eu-alara.net).

Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacy combines glial and vascular injuries in various sequences. Recent studies point out the role of oligodendrocytes and their precusors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypofractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially megatherapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks.

The 11th European ALARA Network (EAN) workshop on “ALARA in radioactive waste management” took place in Athens (Greece) in April 2008. The aim of that workshop was to focus on the implementation of the ALARA principle with regard to occupational and public exposures arising from the management of radioactive waste in all sectors (nuclear, medical, industrial, etc.). This workshop consisted of invited oral presentations, which highlighted the main issues, and half of the programme was devoted to discussions within working groups on specific topics. Individual presentations (papers and slides) are available to download from the EAN website (http://www.eu-alara.net). Based on report backs from the groups and discussions with all the participants, five formal recommendations have been formulated. These recommendations, addressed to international organisations (International Atomic Energy Agency, European Commission, Nuclear Energy Agency), national authorities, national and local stakeholders and to EAN itself, deal with the following themes: international guidance on ALARA in radioactive waste management, harmonisation issues at the international level, ALARA approach in non-nuclear waste management, “broader approach” in the radioactive waste management process, stakeholder involvement. The objective of this paper is to present the main conclusions and the five recommendations produced during the workshop.

Since the beginning of the 90s, EDF has made great efforts to improve ALARA for occupational exposures in the French nuclear power plants. This resulted in the important reduction of the individual doses (581 workers received more than 20 mSv in 1996; in 2006 no one received more than 20 mSv and only 17 received more than 16 mSv) and of the average collective dose per reactor (reduction by more than a factor two in ten years). EDF wishes to continue its efforts. One of the ways of improvement is the analysis of the feedback experience in the foreign power plants having good dosimetric results or with a recent significant improvement of the dosimetric results. Thus, between 2003 and 2006, the CEPN has organized for EDF eight benchmarking visits on the organisation and practical implementation of radiation protection in foreign nuclear power plants. For each visit, a team composed of two representatives from EDF and two representatives from CEPN, goes to the site during a week and meets representatives of services implied in the implementation of the specific topic, which was selected. Several good practices of radiation protection were identified during these visits: the good integration of radiation protection in the management of the plant; the efforts in reducing the source term; the fundamental impact of the reduction of exposed volumes of work through the optimisation of the maintenance programmes and modification of the design reducing the necessity of maintenance; a close and experienced radiological protection; new tools in the service of radiological protection for the 21st century, in particular the use of remote monitoring systems.

The 10th european ALARA network (EAN) workshop took place in Prague (Czech Republic) in September 2006. This was the 10-year anniversary of the EAN, and unlike the previous workshops that addressed a particular ALARA topic, the aim of this workshop was to consider the implementation of the optimisation principle in all domains of activities (nuclear and conventional industry, medical sector, NORM industry). This principle is fundamental to radiation protection, and the workshop drew together key stakeholders to discuss its past, present and future status. The workshop was asked to consider the practical implementation of ALARA, and how this might be improved in the next 10 years. The objectives of the 10th EAN workshop were to review the past evolution of the ALARA concept, internationally, within the EU, and nationally, in terms of the practical impact on radiation protection; to examine the current status of the implementation of the ALARA principle; and to identify needs for future developments in the concept and implementation of optimisation. As with previous workshops, half the programme time was devoted to invited presentations, and half to working group discussions and report backs. After discussion, the output of these working groups was collated by the EAN co-ordinators, to produce seven formal recommendations to international organizations (IAEA, International Labour Organisation, European Commission), to EAN itself and to national authorities. These recommendations deal with justification of practices, holistic approach, ALARA culture, ALARA training, especially in the medical sector, ALARA focus through inspection and control, and stakeholder involvement. Individual presentations (papers and slides) are available to download from the EAN website (http://www.eu-alara.net).