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Deux enquêtes précédentes ont été réalisées en 1995 et 1999 pour évaluer l'utilisation de la radiothérapie dans le traitement d'affections bénignes non-tumorales. En 2016, le même questionnaire a été utilisé et envoyé aux 24 centres du pays : 22 centres ont répondu. Une diminution très importante du nombre de patients a été observée : 360 patients pour l'année 2016 contre 954 en 1999 et 1113 en 1995. Les indications les plus fréquentes restent la prévention des chéloïdes, des formations osseuses hétérotopiques et de la gynécomastie. Une nouvelle indication est apparue : les névralgies du trijumeau traitées par radiochirurgie. La prévention des sténoses coronariennes et le traitement de la dégénérescence maculaire, indications fréquentes dans les enquêtes antérieures, ne sont plus retenus. Un grand consensus est observé concernant les indications potentielles mais aussi dans la non utilisation de la radiothérapie pour les maladies inflammatoires. Two prior surveys were carried out in 1995 and 1999 to evaluate the use of radiotherapy in the treatment of non-malignant disease. In 2016, the same questionnaire was used and sent to the 24 centers of the country: 22 responded. A major decrease was observed in the number of patients treated: 360 in 2016 in contrast to 954 in 1999 and 1113 in 1995. The most frequent indications remain the prevention of heterotopic bone formation, keloids or gynecomastia. A new indication was observed: trigeminal nevralgia treated with radiosurgery. Two frequent indications in the past disappeared: the prevention of coronary restenosis and the macular degeneration. A great agreement was observed regarding the possible indications for radiotherapy but also to avoid it for inflammatory pathologies. [ABSTRACT FROM AUTHOR]

Abstract It is now well demonstrated that (18F)-fluorodeoxyglucose PET/CT is the most accurate imaging method for determining disease extent in Hodgkin lymphoma. Thus, up-front PET/CT is mandatory for involved node radiation therapy design. For a proper use of this new imaging modality for radiotherapy, some adaptations should be made to the PET/CT acquisition as well as to the report. Initial PET/CT should be performed in the radiotherapy treatment position. Nuclear medicine physicians should report to the radiation oncologist the precise location of each involved lymph node, for which the use of a common atlas of upper diaphragmatic nodal stations could be useful. All these new procedures have to be implemented in close collaboration among the different medical specialists providing care to Hodgkin lymphoma patients. We report here the usual procedures of PET/CT acquisition in the radiotherapy environment and propose a more sophisticated description of the different lymph nodes for a more efficient nuclear medicine report to the radiation oncologist. Résumé Il est maintenant clairement établi que la TEP/tomodensitométrie au (18F)-fluorodésoxyglucose est la technique d’imagerie de référence pour le bilan d’extension des lymphomes de Hodgkin. Par conséquent, l’utilisation de la TEP/tomodensitométrie est indispensable pour la réalisation d’une radiothérapie de type involved-node. L’utilisation de cette imagerie fonctionnelle par les radiothérapeutes nécessite une acquisition des images et un compte rendu d’examen particuliers. La TEP préthérapeutique doit être réalisée en position de traitement. Le compte rendu doit décrire précisément l’ensemble des ganglions supposés envahis, raison pour laquelle une classification unique décrivant l’ensemble des aires ganglionnaires sus-diaphragmatiques est proposée. Cette nouvelle technique thérapeutique nécessite une collaboration étroite entre différentes spécialités médicales. Cet article a pour objet la description de la réalisation pratique de la TEP/tomodensitométrie en position de radiothérapie ainsi qu’une trame de compte rendu d’examen prenant en compte la description des différents ganglions sus-diaphragmatiques. [ABSTRACT FROM AUTHOR]

Abstract: This review focuses on the biological functions and signalling pathways activated by Lymphotoxin α (LTα)/Lymphotoxin β (LTβ) and their receptor LTβR. Genetic mouse models shed light on crucial roles for LT/LTβR to build and to maintain the architecture of lymphoid organs and to ensure an adapted immune response against invading pathogens. However, chronic inflammation, autoimmunity, cell death or cancer development are disorders that occur when the LT/LTβR system is twisted. Biological inhibitors, such as antagonist antibodies or decoy receptors, have been developed and used in clinical trials for diseases associated to the LT/LTβR system. Recent progress in the understanding of cellular trafficking and NF-κB signalling pathways downstream of LTα/LTβ may bring new opportunities to develop therapeutics that target the pathological functions of these cytokines. [Copyright &y& Elsevier]

Abstract: In cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality and may precede bacterial colonization. The aim of the present study was to investigate the molecular mechanisms underlying intrinsic inflammation in cystic fibrosis airways. Using different cystic fibrosis cell models, we first demonstrated that, beside a high constitutive nuclear factor of kappaB (NF-κB) activity, CF cells showed a higher activator protein-1 (AP-1) activity as compared to their respective control cells. Gene expression profiles, confirmed by RT-PCR and ELISA, showed over-expression of numerous NF-κB and AP-1-dependent pro-inflammatory genes in CF cells in comparison with control cells. Activation of NF-κB was correlated with higher inhibitor of κB kinase (IKK) activity. In addition, Bio-plex phosphoprotein assays revealed higher extracellular signal-regulated kinase (ERK) phosphorylation in CFT-2 cells. Inhibition of this kinase strongly decreased expression of pro-inflammatory genes coding for growth-regulated proteins (Gro-α, Gro-β and Gro-γ) and interleukins (IL-1β, IL-6 and IL-8). Moreover, inhibition of secreted interleukin-1β (IL-1β) and basic fibroblast growth factor (bFGF) with neutralizing antibodies reduced pro-inflammatory gene expression. Our data thus demonstrated for the first time that the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) at the plasma membrane leads to an intrinsic AP-1, in addition to NF-κB, activity and consequently to a pro-inflammatory state sustained through autocrine factors such as IL-1β and bFGF. [Copyright &y& Elsevier]

Abstract: Background and purpose: To reduce the dose to the heart during left breast irradiation, a moderate deep breath hold technique (MDIBH) was introduced. Originally, verification of the MDIBH was performed with portal images acquired in movie loop during the treatment delivery. However, this verification method is not compatible with the use of dynamic MLC compensation, recently introduced because of its often superior dose distribution. Magnetic sensors were evaluated as an additional/alternative method to monitor the breath hold. Material and methods: In a first phase, the reproducibility of MDIBH for breast patients was evaluated by investigating for 19 patients the set-up errors derived from portal images in cine loop acquisition during MDIBH. In a second phase, for 10 patients, the breathing curves recorded by magnetic sensors were used to monitor beam-on and beam-off while portal images were simultaneously recorded in movie loop. In a third phase, breast patients treated with dynamic MLC compensation were trained for MDIBH and monitored with magnetic sensors. Results: The interfraction reproducibility of MDIBH for the initial 19 patients was recorded: the mean set-up error, the systematic and the random deviations are all smaller than 4mm in the anterior–posterior direction and in the cranio-caudal direction and smaller than 2° along the rotation axis. Magnetic sensors provided a reproducible breathing curve: while the mean amplitude recorded for 10 patients varied substantially between patients, the individual standard deviation of the amplitude for each session was smaller than 3mm. For these 10 patients, the intrafraction set-up variation between the first portal image of two consecutive breath holds and the intra-breath hold set-up variation between the first and last portal image of each breath hold is smaller than 2mm in the anterior–posterior direction, smaller than 3mm in the cranio-caudal direction and smaller than 1.5° along the rotation axis. Conclusion: Using magnetic sensors to record the breathing curve of left breast patients in MDIBH, a verification method was developed, suitable for combining MDIBH with dynamic MLC compensation. [Copyright &y& Elsevier]

: PurposeBetween 1978 and 1998, 533 prostate adenocarcinoma patients were treated with mixed photon-neutron radiotherapy. We report on a retrospective series of patients for whom the side effects of the treatment and their impact on quality of life were assessed by a mailed questionnaire.: Methods and materialsThe European Organization for Research and Treatment of Cancer quality-of-life core questionnaire and a prostate-specific questionnaire were used. Between 1990 and 1996, 308 consecutive patients were treated. Two protocols were used: pelvic fields (50 Gy equivalent photons, 2 Gy/fraction) followed by a prostate boost (66 Gy) or prostate alone. The neutron/photon ratio varied. The questionnaire was mailed to 262 patients presumed to be alive.: ResultsOf the 262 patients, 230 replied. Of the 230 patients, 73% had no trouble doing strenuous activities and 4% had trouble with taking a short walk. The overall physical condition and quality-of-life questions received a mean score of 5.2 and 5.3 on a 7-point scale, respectively. Twenty-two percent had bowel movements at least four times daily, and 6% did so six times or more. Retaining stool was a problem in 26%, and only 38% reported full continence; 17% urinated four times or more nightly. Urinary incontinence was scored as “quite a bit” or “very much” in 11% and 5%, respectively. Hematuria and dysuria (pain) were reported by 7% and 16%, respectively, mainly as moderate. Only 28% reported easy erections, but 75% judged the sexual change acceptable. A greater neutron/photon ratio was significantly associated with more bowel problems (p = 0.003).: ConclusionMixed photon-neutron therapy for prostate cancer was associated with significant patient-reported side effects. Their significant effect on patients'' quality of life is described. [Copyright &y& Elsevier]

: PurposeWe present our ongoing clinical experience utilizing 3D conformal radiation therapy (3D-CRT) to deliver partial-breast irradiation (PBI) in patients with early-stage breast cancer treated with breast-conserving therapy.: Methods and materialsThirty-one patients referred for postoperative radiation therapy after lumpectomy were treated with PBI using our previously reported 3D-CRT technique. Ninety-four percent of patients had surgical clips outlining the lumpectomy cavity (mean: 6 clips). The clinical target volume (CTV) consisted of the lumpectomy cavity plus a 10-mm margin in 9 patients and 15-mm margin in 22 (median: 15 mm). The planning target volume consisted of the CTV plus a 10-mm margin for breathing motion and treatment setup uncertainties. The prescribed dose (PD) was 34 or 38.5 Gy (6 patients and 25 patients, respectively) in 10 fractions b.i.d. separated by 6 h and delivered in 5 consecutive days. Patients were treated in the supine position with 3–5 beams (mean: 4) designed to irradiate the CTV with <10% inhomogeneity and a comparable or lower dose to the heart, lung, and contralateral breast compared with standard whole-breast tangents. The median follow-up duration is 10 months (range: 1–30 months). Four patients have been followed >2 years, 6 >1.5 years, and 5 >1 year. The remaining 16 patients have been followed <12 months.: ResultsNo skin changes greater than Grade 1 erythema were noted during treatment. At the initial 4–8-week follow-up visit, 19 patients (61%) experienced Grade 1 toxicity and 3 patients (10%) Grade 2 toxicity. No Grade 3 toxicities were observed. The remaining 9 patients (29%) had no observable radiation effects. Cosmetic results were rated as good/excellent in all evaluable patients at 6 months (n = 3), 12 months (n = 5), 18 months (n = 6), and in the 4 evaluable patients at >2 years after treatment. The mean coverage of the CTV by the 100% isodose line (IDL) was 98% (range: 54–100%, median: 100%) and by the 95% IDL, 100% (range: 99–100%). The mean coverage of the planning target volume by the 95% IDL was 100% (range: 97–100%). The mean percentage of the breast receiving 100% of the PD was 23% (range: 14–39%). The mean percentage of the breast receiving 50% of the PD was 47% (range: 34–60%).: ConclusionsUtilizing 3D-CRT to deliver PBI is technically feasible, and acute toxicity to date has been minimal. Additional follow-up will be needed to assess the long-term effects of these larger fraction sizes on normal-tissue sequelae and the impact of this fractionation schedule on treatment efficacy. [Copyright &y& Elsevier]

: PurposeA CT-based three-dimensional (3D) method was used to analyze the intra- and interfraction reproducibility of lung immobilization during moderate deep inspiration breath hold (mDIBH), defined as 75% of the maximal inspiration using an active breathing control (ABC) apparatus.: Methods and materialsThe ABC apparatus was used to immobilize the breathing motion with a computer-controlled valve. Immobilization of the lungs in breast cancer patients was used as a model to evaluate the reproducibility of mDIBH using the ABC apparatus. CT scans were acquired twice at mDIBH in the same session for 30 breast cancer patients. Twenty-three of them were immobilized with an α-cradle, of which 14 had a repeat scan at mDIBH 1–4 weeks later. Twelve of those patients received intensity-modulated radiotherapy to the left breast at mDIBH to displace the heart from the beam. The remaining patients were treated at free breathing, with either intensity-modulated irradiation to the whole breast or conformal partial breast irradiation. To remove the component of setup error, mDIBH scans were registered with respect to the vertebrae. The lungs and carina were auto-contoured to form 3D surfaces for each data set. The closest distance-to-agreement (DTA) for each point between the 3D surfaces of the corresponding CT scans was displayed on a 3D surface map. For analysis, each lung was divided along its inferior to superior extent into six regions, from the basal 10%, the next four consecutive 20% sections in height, to the last apical 10%. Likewise, the carina was divided into regions of the trachea and bifurcation. The mean and standard deviation (SD) of the DTA for each of these regions was computed.: ResultsWith the patient positioned in an α-cradle, the mean ± SD intrafraction DTA was 1.5 ± 1.4 mm for the left lung and 1.0 ± 1.4 mm for the right lung. The corresponding values without the use of an α-cradle were significantly greater, with 1.9 ± 2.1 mm and 2.2 ± 2.2 mm for the left and right lung, respectively (p <0.005 for the SD of the left lung and p <0.0003 for the SD of the right lung). The interfraction DTA for the left and right lungs was 1.4 ± 1.7 mm and 1.4 ± 1.6 mm, respectively. The regional analysis demonstrated better immobilization for the upper two-thirds of the chest wall compared with that for the lung base. The DTA values obtained for the tracheal bifurcation were 0.9 ± 0.8 mm for intrafraction and 1.4 ± 1.0 mm for interfraction.: ConclusionThe ABC device can be used to reduce respiratory motion at mDIBH in breast cancer patients or those patients who can perform the maneuver. This device demonstrated excellent intra- and interfraction reproducibility of chest wall and carina immobilization, especially when combined with α-cradle immobilization. Internal margins for suspended breathing can be extrapolated from these data for various anatomic regions within the lung and chest wall. [Copyright &y& Elsevier]

: IntroductionWe present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast.: Methods and materialsBetween February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. “Step-and-shoot” intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary.: ResultsA comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart V30) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4–6 per treatment) with a median duration of 22 s per breath hold (range: 10–26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13–32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1°, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1°, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD).: ConclusionReduction in heart V30 can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed.Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy [Copyright &y& Elsevier]

Purpose: To evaluate the heart and lung sparing effects of moderate deep inspiration breath hold (mDIBH) achieved using an active breathing control (ABC) device, compared with free breathing (FB) during treatment with deep tangents fields (DT) for locoregional (LR) irradiation of breast cancer patients, including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH technique to other standard techniques and to evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT).Methods and Materials: Fifteen patients (9 left-sided and 6 right-sided lesions) with Stages 0–III breast cancer underwent standard FB and ABC computed tomographic (CT) scans in the treatment position. A dosimetric planning study was performed. In FB, the 9 left-sided patients were planned with a 5-field technique where electron fields covering the IM region were matched to shallow tangents using wedges (South West Oncology Group [SWOG] protocol S9927 technique A). This method was compared with a 3-field DT technique covering the breast and the IMNs (SWOG S9927 technique B). Compensation with IMRT was then compared with wedges for each technique. For the 15 total patients, dosimetric planning using DT with IMRT was then reoptimized on the mDIBH CT data set for comparison. Dose-volume histograms for the clinical target volume (CTV) (including the IMNs), planning target volume (PTV), ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In addition, normal tissue complication probabilities (NTCP) for lung and heart, mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were compared.Results: For the 9 left-sided patients, the mean percentage of heart receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique than with the DT wedged technique (6.8% and 19.1%, respectively, p < 0.004). For the DT technique, the replacement of wedges with IMRT slightly diminished the mean heart V30 to 16.3% (p < 0.51). The introduction of mDIBH to the DT-IMRT technique reduced the heart V30 by 81% to a mean of 3.1% (p < 0.0004). Compared with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9 patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT-IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5-field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from 20.4% to 15.2% (p < 0.00007). With DT-IMRT, more than 5% of the contralateral breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields. The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was 36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose in all the DT plans but one (99.1% of the volume covered). DT-wedges required more MUs than DT-IMRT (mean of 645 and 416, respectively, p < 0.00004).Conclusion: mDIBH significantly reduces heart and lung doses when DT are used for LR breast irradiation including the IMNs. Compared with shallow tangents matched with electrons, DT with mDIBH reduces the heart dose (in most patients) and results in comparable lung toxicity parameters, but may increase the dose to the contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose to the heart, and diminishes the number of MUs required. [Copyright &y& Elsevier]

L'utilisation de la radiothérapie dans la prise en charge des affections non cancéreuses reste l'objet de controverses, mais a aussi varié au cours des dernières décennies. Nous avons voulu établir un état de la situation actuelle en Belgique. Deux enquêtes précédentes ont été réalisées en 1995 et 1999 ; en 2016 le même questionnaire a été utilisé et envoyé aux 24 centres du pays. Vingt-deux centres ont répondu. Une diminution très importante du nombre de patients pris en charge a été observée : 364 patients en 2016, contre 961 en 1999 et 1118 en 1995. Les indications les plus fréquentes restaient la prévention des chéloïdes, des formations osseuses hétérotopiques et de la gynécomastie. Une nouvelle indication est apparue : les névralgies du trijumeau, traitées par radiochirurgie. Les traitements de l'exophtalmie maligne et des formations osseuses hétérotopiques étaient en net recul, passant de 79 et 232 patients en 1999 à 13 et 73 en 2016 ; 17 centres les considéraient toujours comme une indication potentielle. La prévention des sténoses coronariennes et le traitement de la dégénérescence maculaire, indication fréquente dans les enquêtes antérieures, n'étaient plus retenus et aucun patient atteint de verrues n'a été traité. Les affections inflammatoires n'étaient plus envisagées comme une indication possible, exceptée l'épine calcanéenne (un seul patient a été pris en charge). Le schéma de radiothérapie pour la prévention des formations osseuses hétérotopiques était assez homogène : une irradiation préopératoire de 7 ou 8 Gy. Les chéloïdes étaient prises en charge par curiethérapie ou par radiothérapie externe avec une grande variabilité dans les schémas et doses : en curiethérapie, 10 à 18 Gy en deux ou trois fractions et de 7 à 20 Gy en une seule séance ou dix fractions pour la radiothérapie externe. Le recours aux irradiations pour le traitement des affections bénignes est en net recul en Belgique, mais avec un grand consensus concernant les indications acceptées. [ABSTRACT FROM AUTHOR]

We report the case of a 50-year old women with an oncological history of metastatic breast carcinoma who underwent lung stereotactic body radiation therapy (SBRT) of 60 Gy in 8 fractions for a left upper lobe metastatic lesion. Seven months later, she complains about hoarseness and weakness of voice. Tumoral relapse and other frequent etiologies were excluded. The diagnosis of radiation induced left recurrent laryngeal nerve paralysis causing left vocal cord paralysis (VCP) was made. The symptomatology did not improve till the disease progression and death of the patient 29 months after SBRT. VCP after lung SBRT is a rare adverse event that has not yet been well described in the medical literature. [ABSTRACT FROM AUTHOR]

Objective A national project to improve the quality of breast radiation therapy was started, named PROCAB (PROject on CAncer of the Breast). One of the objectives was to reach a national consensus guideline for the delineation of the regional lymph node areas in breast radiation therapy. Methods The realization of the new guidelines was a step by step process that started with multiple expert meetings where the existing guidelines were analyzed and the delineations of the lymph node regions were performed together with a surgeon, specialized in the anatomy of the drainage of the breast. Results The delineation guidelines are vessel-based. Since the occurrence of pathological lymph nodes is typically around the veins, the cranial and caudal borders of all different nodal regions are based on a 5 mm margin around the veins, except for the parasternal lymph node area. Compared to the existing guidelines there are some major changes. Conclusion With this project a national as well as a European (ESTRO) consensus guideline for the delineation of the regional lymph node areas in breast RT is reached. The new delineation atlas is vessel-based and no longer field-based. [ABSTRACT FROM AUTHOR]

Abstract: As a wide variety of pro-inflammatory cytokines are involved in the development of rheumatoid arthritis (RA), there is an urgent need for the discovery of novel therapeutic strategies. Among these, the inhibition of the NF-κB inducing kinase (NIK), a key enzyme of the NF-κB alternative pathway activation, represents a potential interesting approach. In fact, NIK is involved downstream of many tumor necrosis factor receptors (TNFR) like CD40, RANK or LTβR, implicated in the pathogenesis of RA. But, up to now, the number of reported putative NIK inhibitors is extremely limited. In this work, we report a virtual screening (VS) study combining various filters including high-throughput docking using a 3D-homology model and ranking by using different scoring functions. This work led to the identification of two molecular fragments, 4H-isoquinoline-1,3-dione (5) and 2,7-naphthydrine-1,3,6,8-tetrone (6) which inhibit NIK with an IC50 value of 51 and 90μM, respectively. This study opens new perspectives in the field of the NF-κB alternative pathway inhibition. [Copyright &y& Elsevier]

Stereotactic body radiation therapy is still controversial for inoperable patients with central lung lesion. We report the case of a 59-year-old woman with previous history of head and neck squamous cell carcinoma who was treated by lung stereotactic body irradiation for an inoperable lymph node in station 10R. One year after, a fibroscopy showed a necrosis of the right main bronchus mucosae and the CT showed a radio-induced aneurysm protruding into the right inferior lobular bronchus. The patient eventually died a few hours later with a massive haemoptysis. This case highlights the potential toxicity of central lung stereotactic body radiation therapy and raises the question of its legitimacy. [ABSTRACT FROM AUTHOR]

Background and purpose Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI). Materials and methods Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy. Results DIBH was able to reduce ( p < 0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH ( p < 0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH. Conclusions This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI. [ABSTRACT FROM AUTHOR]

Background and purpose Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. Material and methods During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. Results Borders of the CTV encompassing a 5 mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. Conclusion The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency. [ABSTRACT FROM AUTHOR]

Summary Background Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. Methods Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT02295033 . Findings Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17·2 years (IQR 13·0–19·0). 20-year overall survival was 59·7% (99% CI 56·3–63·0) in the boost group versus 61·1% (57·6–64·3) in the no boost group, hazard ratio (HR) 1·05 (99% CI 0·92–1·19, p=0·323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0·65 (99% CI 0·52–0·81, p<0·0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16·4% (99% CI 14·1–18·8) in the no boost group versus 12·0% (9·8–14·4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1·8% (99% CI 1·1–2·5) in the no boost group versus 5·2% (99% CI 3·9–6·4) in the boost group (p<0·0001). Interpretation A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. Funding Fonds Cancer, Belgium. [ABSTRACT FROM AUTHOR]

Purpose To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (Pr IN ) versus an end-expiratory phase (Pr EX ). Patients and methods Twenty patients underwent CT-simulation in Pr IN and Pr EX . Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05 Gy in 15 fractions and maximal sparing of the organs at risk. Dose–volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. Results Pr IN consistently reduced ( P < 0.001) heart and left anterior descending coronary artery dose metrics compared to Pr EX . Population averages for maximum and mean heart dose were 6.2 Gy and 1.3 Gy for Pr IN versus 21.4 Gy and 2.5 Gy for Pr EX , respectively. Moreover, a maximum heart dose less than 10 Gy was achieved in 80% of patients for Pr IN . Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. Conclusions Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we aimed to build a 3D-model of NIK and to study the binding of pyrazolo[4,3-c]isoquinolines with a view to highlight the structural elements responsible for their inhibitory potency. However, in the course of this work, we unexpectedly found that the pyrazolo[4,3-c]isoquinolines initially reported as NIK inhibitors were neither inhibitors of this enzyme nor of the alternative NF-κB pathway, but were in fact inhibitors of another kinase, the TGF-β activated kinase 1 (TAK1) which is involved in the classical NF-κB pathway. [Copyright &y& Elsevier]

Abstract: Purpose: This work describes the clinical validation of an automatic segmentation algorithm in CT-based radiotherapy planning for prostate cancer patients. Material and methods: The validated auto-segmentation algorithm (Smart Segmentation, version 1.0.05) is a rule-based algorithm using anatomical reference points and organ-specific segmentation methods, developed by Varian Medical Systems (Varian Medical Systems iLab, Baden, Switzerland). For the qualitative analysis, 39 prostate patients are analysed by six clinicians. Clinicians are asked to rate the auto-segmented organs (prostate, bladder, rectum and femoral heads) and to indicate the number of slices to correct. For the quantitative analysis, seven radiation oncologists are asked to contour seven prostate patients. The individual clinician contour variations are compared to the automatic contours by means of surface and volume statistics, calculating the relative volume errors and both the volume and slice-by-slice degree of support, a statistical metric developed for the purposes of this validation. Results: The mean time needed for the automatic module to contour the four structures is about one minute on a standard computer. The qualitative evaluation using a score with four levels (“not acceptable”, “acceptable”, “good” and “excellent”) shows that the mean score for the automatically contoured prostate is “good”; the bladder scores between “excellent” and “good”; the rectum scores between “acceptable” and “not acceptable”. Using the concept of surface and volume degree of support, the degree of support given to the automatic module is comparable to the relative agreement among the clinicians for prostate and bladder. The slice-by-slice analysis of the surface degree of support pinpointed the areas of disagreement among the clinicians as well as between the clinicians and the automatic module. Conclusion: The efficiency and the limits of the automatic module are investigated with both a qualitative and a quantitative analysis. In general, with efficient correction tools at hand, the use of this auto-segmentation module will lead to a time gain for the prostate and the bladder; with the present version of the algorithm, modelling of the rectum still needs improvement. For the quantitative validation, the concept of relative volume error and degree of support proved very useful. [Copyright &y& Elsevier]

Abstract: Background and purposes: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing radiotherapy for prostate cancer requires a standardisation of target delineation as well as clinical quality assurance procedures. Patients and methods: Pathological and imaging studies provide valuable information on tumour extension. In addition, clinical investigations on patient positioning and immobilisation as well as treatment verification data offer an abundance of information. Results: Target volume definitions for different risk groups of prostate cancer patients based on pathological and imaging studies are provided. Available imaging modalities, patient positioning and treatment preparation studies as well as verification procedures are collected from literature studies. These studies are summarised and recommendations are given where appropriate. Conclusions: On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group this article presents a common set of recommendations for external beam radiotherapy of patients with prostate cancer. [Copyright &y& Elsevier]

: PurposeThe active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT).: Methods and materialsTen patients with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans.: ResultsThe medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing.: ConclusionsThe dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment. [Copyright &y& Elsevier]

Purpose: We present a novel three-dimensional conformal radiation therapy (3D-CRT) technique to treat the lumpectomy cavity, plus a 1.5-cm margin, in patients with early-stage breast cancer and study its clinical feasibility.Methods and Materials: A 3D-CRT technique for partial-breast irradiation was developed using archived CT scans from 7 patients who underwent an active breathing control study. The clinical feasibility of this technique was then assessed in 9 patients who were prospectively enrolled on an Investigational Review Board-approved protocol of partial-breast irradiation. The prescribed dose was 34 Gy in 5 patients and 38.5 Gy in 4 patients, delivered in 10 fractions twice daily over 5 consecutive days. The impact of both breathing motion and patient setup uncertainty on clinical target volume (CTV) coverage was studied, and an appropriate CTV-to-PTV (planning target volume) margin was calculated.Results: By adding a CTV-to-PTV “breathing-only” margin of 5 mm, 98%–100% of the CTV remained covered by the 95% isodose surface at the extremes of normal inhalation and normal exhalation. The “total” CTV-to-PTV margin employed to accommodate organ motion and setup error (10 mm) was found to be sufficient to accommodate the observed uncertainty in the delivery precision. Patient tolerance was excellent, and acute toxicity was minimal. No skin changes were noted during treatment, and at the initial 4–8-week follow-up visit, only mild localized hyperpigmentation and/or erythema was observed. No instances of symptomatic radiation pneumonitis have occurred.Conclusions: Accelerated partial-breast irradiation using 3D-CRT is technically feasible, and acute toxicity to date has been minimal. A CTV-to-PTV margin of 10 mm seems to provide coverage for most patients. However, more patients and additional studies will be needed to validate the accuracy of this margin, and longer follow-up will be needed to assess acute and chronic toxicity, tumor control, and cosmetic results. [Copyright &y& Elsevier]

Objectifs Évaluer les pratiques de radiothérapie dans la prise en charge des lymphomes de Hodgkin localisés. Matériel et méthodes À l’initiative d’un groupe pluridisciplinaire, TEP-RT-Hodgkin, un questionnaire centré sur les concepts de volumes cibles ( nodal , involved field et involved site ) et la TEP en position de traitement a été envoyé dans 35 centres académiques français, par le biais de la Société française de radiothérapie oncologique (SFRO). Résultats Vingt-huit centres (80 %) ont répondu, soignant moins de cinq patients par an pour 11 % d’entre eux, de cinq à dix pour 29 %, de dix à 20 pour 46 % et plus de 20 pour 14 %. Les oncologues radiothérapeutes avaient 19,0 ± 9,8 ans d’expérience, dont 14,9 ± 10,1 dans la prise en charge des lymphomes de hodgkin, et 61 % d’entre eux avaient participé à l’essai H10. Quatre-vingt-six pour cent se disaient à l’aise avec les trois concepts. Quinze ont déclaré considérer le nodal comme un standard et l’utiliser en routine. Cinq ont répondu que l’ involved field constituait le standard, hors essai. Huit recouraient à l’ involved site . Cinquante pour cent des oncologues radiothérapeutes ayant participé à l’essai H10 pratiquaient le nodal en routine. À l’inverse, 50 % de ceux n’ayant pas participé à l’essai l’avaient instauré en traitement standard. Si tous utilisaient la tomographie par émission de positons (TEP) pour définir les volumes cibles, 19 réalisaient des TEP en position de traitement. Trois avaient un accès difficile à cet examen et six pas d’accès. Dans cinq centres, les patients étaient référés après chimiothérapie et donc sans possibilité de la réaliser. Si la plupart a déclaré avoir une collaboration avec un médecin nucléaire, quinze oncologues radiothérapeutes se sont dits intéressés par la création d’un réseau de relecture des TEP. Conclusion Hors essai, la définition des volumes et l’accès à la TEP en position de traitement sont hétérogènes. Afin d’harmoniser les pratiques, le groupe prépare des recommandations sur la réalisation de la TEP et la prise en charge des patients. [ABSTRACT FROM AUTHOR]