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Purpose A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. Material and methods Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. Results Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. Conclusion A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

In 2021, the Ethics Commission of the SFRO has chosen the issue of the practice of palliative care in radiotherapy oncology. Radiation oncology plays a central role in the care of patients with cancer in palliative phase. But behind the broad name of palliative radiotherapy, we actually find a large variety of situations involving diverse ethical issues. Radiation oncologists have the delicate task to take into account multiple factors throughout a complex decision-making process. While the question of the therapeutic indication and the technical choice allowing it to be implemented remains central, reflection cannot be limited to these decision-making and technical aspects alone. It is also a question of being able to create the conditions for a singularity focused care and to build an authentic care relationship, beyond technicity. It is through this daily ethical work, in close collaboration with patients, and under essential conditions of multidisciplinarity and multiprofessionalism, that our fundamental role as caregiver can be deployed.

Rectal adenocarcinoma is a quite radioresistant tumor. In order to achieve non-operative management (NOM) radiotherapy plays a major role. Targeted radiotherapy aiming at high precision 3D radiotherapy uses stereotactic image-guided external beam radiotherapy machines. To further safely increase the tumor dose, endocavitary brachytherapy (ECB) is an original approach. There are two different ways to perform such an ECB: contact X-ray brachytherapy (CXB) using a 50 kV X-ray generator with an X-ray tube positioned under eye guidance into the rectal cavity and high-dose-rate brachytherapy (HDRB) using iridium-192 sources positioned into the rectal cavity under image guidance. This study focused on CXB. CXB uses a small mobile generator that produces 50 kV X-rays with limited penetration. This technique is well adapted to accessible tumors of limited size and especially needs a high dose rate (≥15 Gy/minutes) for rectal tumors. It is performed on an ambulatory basis. A total dose between 80–110 Gy is delivered in 3–4 fractions over 3 to 6 weeks into a small volume (5 cm3). CXB was pioneered in the 1970s by Papillon using the Philips RT 50TM. Since 2009, the Papillon P50TM has been used in 11 institutions in Europe. The OPERA Phase III trial tested the hypothesis that a CXB boost (90 Gy/3 fr) compared to an EBRT boost (9 Gy/5 fr) for T2–T3 ab < 5 cm and N0–N1 < 8 mm will increase the 3-year organ preservation (OP) rate when combined with 45 Gy/5 weeks with concomitant capecitabine. Out of more than 300 patients with tumors < 3 cm (1962–1992), Papillon reported a long-term local control close to 85%. Similar results were published in Europe and USA at that time. The Lyon R96-2 Phase III trial (2004) demonstrated that, when combined with preoperative EBRT, a CXB boost (90 Gy/3 fr) significantly increased the rate of clinical complete response (cCR) and sphincter preservation, with some patients having OP at 10 years. With more than 2000 patients treated in Europe (2010–2020) using the Papillon 50TM, organ preservation appears possible in close to 80% of cases in selected early T2–T3. The OPERA trial closed after 141 inclusions (2015–2020) after an independent data monitoring committee recommendation because of promising results. At the 2-year follow-up (blinded data), the rate of cCR and OP were 77% and 72%, respectively, for the 141 tumors, and for T < 3 cm (61 pts), they were 86% and 85%, respectively, with good bowel function. The final results should be available in 2022. Organ preservation using NOM appears to be a promising approach for rectal cancer. A CXB boost with chemoradiotherapy in selected early T2–T3 could become an attractive option to achieve a planned OP. This approach should be proposed to well-informed patients after discussion in an MDT.

Neoadjuvant chemoradiotherapy (nCRT) and watch-and-wait policy as reported by Habr-Gama are references for organ preservation in rectal cancer. To increase the clinical complete response (cCR) and reduce the local recurrence rates, we report a retrospective analysis of a prospective cohort of selected T2-3 tumours treated in three French institutions using contact X-ray brachytherapy (CXB) with nCRT.Tumour selection was based on digital rectal examination (DRE), rigid rectoscopy, magnetic resonance imaging (MRI) and/or endorectal ultrasound. Adenocarcinoma T2-35 cm largest diameter, M0 were treated, all with organ preservation intent. CXB delivering 90 Gy/3 fractions/4 weeks was combined with CRT (capecitabine 50). Strict evaluation of tumour response using DRE and rectoscopy ± MRI was performed at regular interval with prolonged surveillance.Between 2002 and 2016, 74 consecutive patients were treated (median age: 74 years. T2: 45 and T3: 29). A cCR or near-cCR (mainly rectal wall ulceration) was noted at week 14 in 71 patients (95%). A local excision was performed in 13 patients. Of three partial responses (PRs), one salvage anterior resection was performed. With a median follow-up of 3 years, local recurrence (mainly in the rectal wall) was seen in seven patients. The 3-year local recurrence rate was 10%, and the cancer-specific survival, 88%. Two patients underwent radical proctectomy for PR or local recurrence and 96% preserved their rectum. Grade III acute toxicity was recorded in five patients. Rectal bleeding was the main late toxicity (grade III in 12%). Bowel function was scored as good or excellent in 85% of patients.Combining CXB and nCRT in selected early T2-T3 rectal cancers may safely provide a high rate of cCR, organ preservation, and good bowel function with a risk of local recurrence below 15%. Such an approach could be offered to operable patients as a planned option for organ preservation.

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

Resume En 2019, le bureau de la Societe francaise de radiotherapie oncologique (SFRO) a cree une commission ethique. Sa mission est de proposer a notre communaute professionnelle des elements de reflexion a propos de questionnements ethiques, et d’en degager les specificites au sein des services d’oncologie radiotherapie. A l’occasion du congres annuel de 2020, la commission s’est penchee sur l’evolution de la relation soigne-soignant, et plus particulierement sur l’idee forte de partenariat patient. En effet, la redaction du Livre blanc du cancer a donne la parole aux personnes malades et souligne la necessite de nouveaux dispositifs, tels que le « temps d’accompagnement soignant ». Les patients ne peuvent plus etre consideres comme des objets de soin mais comme des personnes dont la dignite et l’autonomie doivent etre imperativement respectees. L’acquisition de connaissances autorise un echange bilateral, prerequis de la dynamique collaborative. Ils peuvent etre partenaires de leurs propres soins, partenaires de la formation et de la recherche (patient expert) mais egalement partenaires des institutions et politiques de sante. C’est cette notion de partenariat et d’implication de la personne dans son parcours de soin en oncologie radiotherapie que nous allons analyser ici. Il s’agira autant de la definir, en developpant la notion d’autonomie, que d’en faire emerger la complexite et l’ambivalence au travers notamment de deux exemples issus de notre pratique clinique : la demarche de decision partagee pour les patients ayant un cancer de la prostate localise et l’implication du patient dans le bon deroulement de sa radiotherapie.

Purpose Iodine-125 (125I) seeds can be used as landmarks to locate non-palpable breast lesions instead of implanting metal wires. This relatively new technique requires a nuclear probe usually used for technetium-99m (99mTc) sentinel node detection. This study aimed to compare the performances of different probes and valid the feasibility of this technique, especially in the case of simultaneous 125I-seed and 99mTc breast cancer surgery. Methods Three probes with different features (SOE-3211, SOE-3214 and GammaSUP-II) were characterised according to the NEMA NU3-2004 standards for a 99mTc source and a 125I-seed. Several tests such as sensitivity, linearity or spatial resolution allowed an objective comparison of their performances. NEMA testing was extended to work on signals discrimination in case of simultaneous detection of two different sources (innovative figure of merit “Shift Index”) and to assess the 99mTc scatter fraction, a useful parameter for the improvement of the probes in terms of detector materials and electronic system. Results Although the GammaSUP-II probe saturated at a lower activity (1.6 MBq at 10 mm depth), it allowed better sensitivity and spatial resolution at the different NEMA tests performed with the 99mTc source (7865 cps/MBq and 15 mm FWHM at 10 mm depth). With the 125I-seed, the GammaSUP-II was the most sensitive probe (3106 cps/MBq at 10 mm depth) and the SOE-3211 probe had the best spatial resolution (FWHM 20 mm at 10 mm depth). The SOE-3214 probe was more efficient on discriminating 125I from 99mTc in case of simultaneous detection. The SOE probes were more efficient concerning 99mTc scatter fraction assessments. The SOE-3211 probe, with overall polyvalent performances, seemed to be an interesting trade-off for detection of both 125I and 99mTc. Conclusion The three probes showed heterogeneous performances but were all suitable for simultaneous 99mTc sentinel node and 125I-seed detection. This study provides an objective and innovative methodology to compare probes performances and then choose the best trade-off regarding their expected use.

Contact X ray brachytherapy 50 kVp was initiated in the 1930s with the Siemens unit and popularized with the Philips unit in the 1950s. A renaissance was seen in the early 2000s with the Intrabeam™ unit for breast IORT. Presently the Papillon™ systems thanks to its high dose rate (> 10 Gy/mn) can be used to treat breast (IORT), skin, eyelid and rectal cancers. Future developments are expected to consolidate the place of contact radiotherapy as a safe and efficient treatment for accessible early tumors.

A new deterministic method for calculating the dose distribution in the electron radiotherapy field is presented. The aim of this work was to validate our model by comparing it with the Monte Carlo simulation toolkit, GEANT4. A comparison of the longitudinal and transverse dose deposition profiles and electron distributions in homogeneous water phantoms showed a good accuracy of our model for electron transport, while reducing the calculation time by a factor of 50. Although the Bremsstrahlung effect is not yet implemented in our model, we propose here a method that solves the Boltzmann kinetic equation and provides a viable and efficient alternative to the expensive Monte Carlo modeling.

Introduction To evaluate the Delta4 Discover behavior during the VMAT treatments deliverance and to determine the error detection thresholds. Methods The transmission detector Discover (Scandidos) is placed at the exit of the beam on Clinac 2100C Varian with Millenium MLC 120 leaves. It is composed of 4040 diodes with a 1 mm diameter, spaced 5 mm perpendicularly to the leaves movement and 2.5 mm in the same direction than the leaves movement and covering a 19.5 cm x 25 cm field size. The attenuation has been measured with 6 and 18MV beams at isocenter (field size 10 cm x 10 cm at a depth of 10 cm). The system repeatability has been evaluated to control 3 VMAT treatment plans. It was also measured by sequentially inserting different errors like leaves position, change of energy, depth, thickness and patient positioning. The errors of leaves position have been inserted for 3 leaves pairs on 4 control points of each beam. The following parameters can be analyzed: -The index gamma of dose distribution (3%-3 mm) -The delivered dose in function of angulation gantry ( Δ = ± 1%) -The angulation collimator ( Δ = ± 1°) -The MLC index gamma: the beam signal integrated every 25 ms measuring the gantry angulation and the end leaves position. Download : Download high-res image (46KB) Download : Download full-size image Results The measured attenuation is 1.6% in 6MV and 0.9% in 18MV. The repeatability results show an average standard deviation of 0.7% and maximum at 1.6% for 3 treatment plans with gamma index calculation. The results systematically decrease of more than 80% in the gamma index score when the energy of treatment plans has been changed. The results bring out a difference from −6% to −8% with gap of leaves position superior at 2 mm on a beam with 12 inserted mistakes: -5 are > 2 mm -5 are between 1 mm and 2 mm -2 are 1 mm The leaves whose positions are not those expected are correctly identified. Conclusions The Discover system is an advantage for pre- and per-treatment control of patients treated with VMAT. The attenuation modeling directly in the TPS is also an advantage for a daily use on the entire treatment. All measured parameters may show discrepancies or predict premature wear of certain components of the collimator.

Resume Le traitement de reference des carcinomes epidermoides du canal anal localement evolues (stades II et III) est la chimioradiotherapie exclusive. Celle-ci delivre une dose de 45 Gy a raison de cinq fractions de 1,8 Gy par semaine dans un volume pelvien, puis un complement de dose de 14 a 20 Gy dans la tumeur. La chimiotherapie concomitante la plus souvent utilisee comprend une association de 5-fluoro-uracile et de mitomycine-C delivree lors de la premiere et cinquieme semaine d’irradiation. Une couverture optimale des volumes cibles est parfois difficile a obtenir avec une irradiation conformationnelle (jonctions des faisceaux, combinaison d’electrons et photons parfois complexes dans les aires ganglionnaires). La toxicite cutaneomuqueuse et digestive induite par le traitement peut necessiter un intervalle libre avant la realisation du complement d’irradiation. Celui-ci peut avoir un effet deletere sur les resultats s’il est prolonge (plus de 38 jours). Les differentes techniques de radiotherapie conformationnelle avec modulation d’intensite (statique segmentee, dynamique, arctherapie volumique modulee et tomotherapie helicoidale) ont leur interet dans cette localisation. Elles permettent d’obtenir une sterilisation tumorale et ganglionnaire avec une baisse des doses intermediaires et elevees aux organes a risque (intestin grele, perinee/organes genitaux, vessie, moelle osseuse) entrainant une reduction de la toxicite aigue de grade 3 ou plus ainsi qu’une meilleure conservation fonctionnelle du sphincter anorectal. Une description de la realisation de l’arctherapie volumique modulee est presentee dans cet article. Les avantages et inconvenients de cette technique par rapport aux autres y sont discutes.

Background:Major depressive disorder (MDD) is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and associated with excess mortality. Treatments for this disease are not effective in all patients showing the need to find new therapeutic targets.Objective:This review aims to update our knowledge on the involvement of astroglial gap junctions and hemichannels in MDD and to show how they have become potential targets for the treatment of this pathology.Methods:The method applied in this review includes a systematic compilation of the relevant literature.Results and Conclusion:The use of rodent models of depression, gene analysis of hippocampal tissues of MDD patients and post-mortem studies on the brains from MDD patients suggest that astrocytic gap junction dysfunction may be a part of MDD etiologies. Chronic antidepressant treatments of rats, rat cultured cortical astrocytes and human astrocytoma cell lines support the hypothesis that the up-regulation of gap junctional coupling between astrocytes could be an underlying mechanism for the therapeutic effect of antidepressants. However, two recent functional studies suggest that connexin43 hemichannel activity is a part of several antidepressants’ mode of action and that astrocyte gap junctional intercellular communication and hemichannels exert different effects on antidepressant drug response. Even if they emerge as new therapeutic targets for new and more active treatments, further studies are needed to decipher the sophisticated and respective role of astrocytic gap junctions and hemichannels in MDD.

Introduction et but de l’etude Le traitement des adenocarcinomes du rectum de stade T2-3 M0 est la proctectomie totale precedee d’une chimioradiotherapie. En cas de reponse clinique complete une surveillance (watch & wait) ou une exerese locale sont des options pour ameliorer la qualite de vie. L’essai randomise de Lyon R96-02 a demontre qu’en associant la radiotherapie externe et la radiotherapie de contact, les chances de reponse clinique complete sans toxicite augmentaient [1] . Depuis 2010, il y a un regain de recours a la radiotherapie de contact avec l’utilisation de l’appareil Papillon50™. Materiel et methodes De 2003 a 2016, 74 malades atteints de cancer de stade M0 ont ete pris en charge par radiotherapie de contact et chimioradiotherapie a Lyon, Mâcon et Nice. L’âge median des patients etait de 74 ans, la tumeur de stade T2 pour 45 patients, et T3 pour 29. La classification de la tumeur a ete faite par IRM et/ou echographie endorectale. La chimoradiothepie delivrait 50 Gy, avec de la capecitabine, la radiotherapie de contact delivrait de 90 a 110 Gy en trois ou quatre seances. Si la tumeur ne depassait pas 3,5 cm de diametre le traitement commencait par la radiotherapie de contact. La surveillance etait tous les 3 mois par toucher rectal, rectoscopie rigide et IRM [2] . Resultats et analyse statistique Le taux de reponse clinique compete 6 mois apres le debut du traitement etait de 95 % pour les 74 malades. Les taux de recidive locale a 3 ans et de survie specifique etaient respectivement de 10 % et 88 %. Le taux de conservation rectale etait de 95 % avec une bonne fonction rectale dans 90 % des cas. Parmi les six echecs locaux, aucun n’est survenu pour les lesions de stade T2-T3a polypoides de moins de 3,5 cm de diametre. Lorsque ces lesions etaient traitees par irradiation de contact initiale, une reponse clinique compete a ete observee des la semaine 4 dans 67 % des cas et dans 95 % au troisieme mois (contre 75 % en cas de chimioradiothepie premiere). Conclusion Il est possible de proposer comme option therapeutique une conservation rectale pour les cancers de stade T2 T3a-b de moins de 5 cm de diametre. La probabilite de succes depasse 85 % pour les lesions polypoides de moins de 3,5 cm traitee par irradiation de contact premiere chez qui cette preservation peut etre programmee comme c’est le cas pour les carcinomes epidermoides du canal anal. L’essai randomise Opera en cours devrait permettre de valider cette proposition.

Resume Introduction Les standards actuels d’irradiation de metastases osseuses visent essentiellement a une antalgie et a la prevention du risque fracturaire a court terme. Cependant, l’index therapeutique des nouvelles techniques d’irradiation (doses plus elevees avec epargne des tissus sains) et des traitements combines avec radiologie interventionnelle permet d’envisager un traitement local optimise dans un nombre croissant de situations cliniques. Materiel et methodes Une recherche de la litterature anglaise et francaise a ete effectuee avec les mots cles : metastases osseuses, radiotherapie, radiologie interventionnelle, cimentoplastie, radiofrequence, chimioembolisation. Resultats-discussion Les traitements realises a visee ablative conduisent a des taux de soulagement de la douleur superieurs a 90 % dans des essais de phase I/II et des etudes retrospectives. La stereotaxie, la RCMI (statique, rotationnelle, helicoidale) permettent d’envisager de delivrer des doses elevees dans un objectif de controle local durable (75-90 % a 2 ans) voire de prolongation de la survie. Certaines situations evaluees anterieurement comme strictement palliatives sont actuellement traitees de facon plus maximaliste par des modalites d’irradiation optimisees parfois combinees a une modalite de radiologie interventionnelle. Des situations de metastases etendues pourraient beneficier de techniques optimisees dans un but de preservation des organes sains. Conclusion Les donnees actuelles suggerent, meme en l’absence d’essais randomises pour ces techniques recentes, un service rendu au patient par l’utilisation des techniques conformationnelles de radiotherapie et des traitements combines. Il ne s’agit pas de proposer une recommandation en l’absence de niveau de preuve suffisant mais de refleter la pratique quotidienne rendue possible par les nouvelles techniques d’irradiation dans le sens d’un service rendu au patient tout en integrant une logique economique des soins. L’impact de ces « approches maximalistes » sur la survie reste a demontrer formellement par des etudes prospectives interventionnelles ou des observatoires incluant des criteres de qualite de vie et un recul d’au moins deux ans.

Brachytherapy consists in placing radioactive sources directly in contact with the tumoral bed. The type of source, its characteristics and its use will be adapted regarding the kind of treatment foreseen. Modern brachytherapy techniques employ remote afterloading technologies allowing better quality and security in the delivery of treatment. This development of technology goes with an increase need of quality control of equipments, including radionuclides, and procedures.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Resume Objectif de l’etude Evaluer la faisabilite et la qualite de la tomotherapie helicoidale pour le traitement protocolaire de tumeurs axiales et para-axiales. Patients et methodes Il s’agit d’une etude protocolaire menee a l’institut Bergonie de juin 2007 a juin 2009, ayant permis de colliger les 14 premieres tomotherapies helicoidales chez des patients atteints de tumeurs axiales et para-axiales. Il s’agissait de trois tumeurs paravertebrales (deux sarcomes et une tumeur maligne des gaines des nerfs peripheriques), cinq tumeurs vertebrales primitives (trois tumeurs d’Ewing et deux tumeurs a cellules geantes), six tumeurs sacrees et iliosacrees (quatre chordomes et deux chondrosarcomes). Resultats La dose prescrite a la mediane du volume cible previsionnel a varie en fonction du type histologique de 45 a 68 Gy. Dans les cinq cas ou la tumeur siegeait en regard de la moelle epiniere, la dose a 2 % du volume (D2 %) etait de 40,1 Gy (37,8–45,4). Dans les sept cas ou la tumeur etait situee en regard de la queue de cheval, la dose maximale etait de 46,5 Gy (39,2–60). Dans les deux cas ou le nerf sciatique etait la structure nerveuse a risque, la D2 % etait de 64,4 et 67 Gy. Avec une duree mediane de suivi de 14,5 mois, six patients etaient en situation de remission complete, deux de stabilisation tumorale ; six de recidive, parmi lesquels deux sont decedes avec une progression tumorale locale et metastatique. La tolerance immediate a ete generalement favorable (deux cas de radiodermite de grade 3 selon la CTCAE v3) et aucun traitement n’a ete interrompu. Conclusion Il s’agit donc d’une serie preliminaire confirmant la faisabilite, la bonne tolerance immediate et l’accessibilite de la tomotherapie helicoidale dans cette pathologie.

Langerhans cell histiocytosis is a non-malignant proliferative disease of unknown etiology that can affect one or more organs. This is a rare disease, 1 to 2/100,000, affecting mainly children with a male predominance. The osseous lesions are the most frequent (60 to 90%). There is however no consensus treatment for the management of these sites. We report the cases of two patients successfully treated with radiotherapy after primary chemotherapy, at doses of 15 Gy in ten sessions of 1.5 Gy for one patient and 18 Gy in ten fractions of 1.8 Gy for the other. Single or multifocal bone Langerhans cell histiocytosis without visceral involvement is a benign, self-limiting affection in most cases. Some bone lesions could be treated by radiotherapy alone. But the high variability of doses currently given in the literature does not allow determining the lowest effective dose limiting the risk of secondary neoplasia or impaired growth in children, in whom lower doses of 6 to 8 Gy are recommended. The decision of radiotherapy must be weighed against the risk of the disease. Caution should be the rule in this non-malignant tumour pathology.

Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably underevaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume.

Resume Les plexites et neuropathies peripheriques, d’apparition progressive et tardive apres la radiotherapie, sont principalement observees dans trois circonstances cliniques : les irradiations des regions sus-claviculaires et axillaires pour les cancers du sein, les irradiations lombaires et pelviennes pour des maladies variees et enfin les irradiations des membres pour les sarcomes des tissus mous. Les nerfs peripheriques et les plexus (brachial et lombosacre) sont assimiles a des organes a risque en serie pour lesquels une irradiation au-dela d’une dose seuil peut entrainer une dysfonction de l’ensemble de l’organe. Les donnees de la litterature, souvent anciennes, permettent de fixer pour les plexus une dose tolerable a 60 Gy mais temoignent aussi d’une forte sensibilite au fractionnement et aux fortes doses par fraction. Pour les nerfs peripheriques, les sequelles les plus frequentes sont des douleurs dont la survenue varie significativement entre 50 et 60 Gy. L’importance du terrain (diabete, atteinte vasculaire, neuropathie preexistante…) et des traitements associes (chirurgie, chimiotherapie…) reste peu evaluee malgre un role probablement non negligeable dans la survenue de ces neuropathies radio-induites.

Helical tomotherapy is an innovative device combining with the same linac on board-imaging and IMRT facilities. The first national French evaluations, supported by National Institut of Cancer (INCa) are presented. Dosimetric characteristics as quality of homogeneity, cut-off outside target volumes allow IMRT treatments for large and complex volumes and a good organ at risk sparing. First comparative dosimetric studies are discussed.

751 Background: The Lyon R96-02 randomized trial has demonstrated in T2-3 rectal cancer that external beam radiotherapy (EBRT) with Contact X Ray brachytherapy (CXB) boost was increasing clinical complete response, sphincter preservation and in early cases organ preservation. We report French experience in 3 radiotherapy departments using CXB boost with chemoradiotherapy (CRT) in early T2T3N0. Methods: Selection based on digital rectal examination, colonoscopy, MRI (and/or Endorectal-ultrasound). Inclusion : adenocarcinoma (distal, middle rectum), T2 T3a-b, tumor diameter ≤ 4cm, N0, M0. Treatment : CXB (80-110 Gy/3-4 fr) followed by CRT (CAP 50). Tumor response assess on week 14 : DRE, rigid rectoscopy and MRI. Clinical complete response (cCR) defined as no visible tumor, supple rectal wall and TRG 1-2 on MRI. In case of cCR a close surveillance or local excision was proposed. Results: Between 2002 -2016, 84 patients treated. Median age: 75 years, Male: 59, Female: 25. Operable patients: 69 (83%). T2 : 52, T3 : 32 (Lyon Villeurbanne : 16, Macon : 11, Nice : 57). Median follow-up time : 53 months. cCR was achieved in 94% of cases. Local excision performed in 17 patients (ypT0 : 16). At 4 years, the cancer specific survival was 82% [CI:96-70] and the local relapse rate 12% [CI: 2-22]. No isolated perirectal lymph node relapse observed. After 4 years, 3 more local relapses observed (4, 6, 7 years). Main late toxicity ( > 6 months after treatment) was rectal bleeding (radiation telangiectasia) which required plasma argon coagulation in 5 patients. No TME surgery was performed and organ preservation was achieved in all cases. Bowel function was good in 85% of patients (LARS score < 20). Conclusions: When combining CXB with CRT, rectal cancer T2T3a-b N0 ≤4cm achieve a high rate of cCR (≥85%) with organ preservation, good bowel function, low rate of local relapse ( < 15%) and low toxicity. As rectal adenocarcinoma is radioresistant, the treatment must use a CXB boost. Like anal squamous cell cancer, planned organ preservation can be proposed to operable patients. The ongoing European OPERA trial aims at bringing evidence to this option.

Resume Objectif de l’etude Evaluer les gains dosimetriques apportes par la tomotherapie helicoidale pour le traitement des sarcomes des tissus mous de la cuisse. Patients et methodes Les donnees anatomiques et dosimetriques de trois patients recemment traites par irradiation conformationnelle postoperatoire ont servi de reference. Ces patients etaient atteints d’un sarcome de la loge posterieure, anterieure ou des adducteurs. Pour chacun des traitements, la dosimetrie de reference de la radiotherapie conformationnelle reellement delivree a ete comparee a une dosimetrie de RCMI en mode dynamique avec le meme accelerateur lineaire et a trois dosimetries de tomotherapie selon le mode de blocage (sans blocage, blocage unidirectionnel ou complet du membre controlateral). Resultats La tomotherapie ameliorait la couverture du volume cible previsionnel (PTV) ainsi que son homogeneite de dose, quelle que soit la modalite de planification. En effet, la D95 % (dose representant 95 % de la dose prescrite) moyenne etait de 97,6 % en tomotherapie et de 94,8 % en radiotherapie conformationnelle et l’homogeneite de la dose, evaluee par l’ecart-type de l’histogramme dose-volume differentiel du PTV, etait meilleure d’au moins un facteur 2 qu’en radiotherapie conformationnelle et toujours meilleure qu’en RCMI. Le volume des loges musculaires voisines recevant la totalite de la dose prescrite et les points chauds mesures par la D2 % etaient aussi diminues avec la tomotherapie. Cependant, la protection des autres organes a risque (peau, femur et gonades) etait variable selon la localisation tumorale traitee et n’etait pas amelioree par la tomotherapie. Conclusions La tomotherapie permet d’augmenter la couverture et l’homogeneite de dose du PTV tout en diminuant les fortes doses recues par les loges musculaires voisines. Neanmoins, il n’y a pas de benefice en termes de protection des autres organes a risque sauf contrainte particuliere (comme par exemple, une zone cutanee ou une zone osteoperiostee). D’autres etudes dosimetriques sont necessaires, suivies d’etudes prospectives, pour determiner si les gains dosimetriques peuvent se traduire en terme de benefices cliniques.

Radiotherapy of glial tumors is rapidly evolving with the recent technical and therapeutic progress. About technical aspects, progress in technical imaging and development of non-coplanar conformal and IMRT techniques provide new possibilities for sparing healthy tissue while increasing dose in tumoral volume. Furthermore, functional and molecular imaging are helpful for delineation and for prediction of relapse. Even modest, the actual improvement of survival with radiochemotherapy leads now to new and important developments for clinical research according to clinical data (age, general status), biological data (MGMT promotor methylation and cytogenetic modifications) and technical data (quality of surgery and radiotherapy). Understanding of molecular mechanisms allows for rational targeting or specific pathways of repair, signaling angiogenesis associated with surgery and radiotherapy in a multidisciplinary approach.

After a request for proposal initiated by National Institute against cancer (INCa) in 2005, three French centers in France started tomotherapy in the first semester of 2007. A national policy of evaluation was performed to study the feasibility of this innovative technique and to compare the interest of helicoidal tomotherapy with other modalities of conformal therapy. Common protocols have been designed to facilitate this evaluation. Description of dose, IMRT levels and constraints are achieved according to each selected indication as: sarcoma, head and neck tumors, lung cancer, mesothelioma, bone metastases, anal carcinoma and craniospinal irradiation.

International audience; : Migraine is a common, recurrent, and disabling primary headache disorder with a genetic component which affects up to 20% of the population. One third of all patients with migraine experiences aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms preceding the headache. In the pathophysiology of migraine with aura, activation of the trigeminovascular system from the meningeal vessels mediates migraine pain via the brainstem and projections ascend to the thalamus and cortex. Cortical spreading depression (CSD) was proposed to trigger migraine aura and to activate perivascular trigeminal nerves in the cortex. Quinine, quinidine and the derivative mefloquine are able to inhibit CSD suggesting an involvement of neuronal connexin36 channels in CSD propagation. More recently, CSD was shown to induce headache by activating the trigeminovascular system through the opening of stressed neuronal Pannexin1 channels. A novel benzopyran compound, tonabersat, was selected for clinical trial on the basis of its inhibitory activity on CSD and neurogenic inflammation in animal models of migraine. Interestingly, in the time course of animal model trials, tonabersat was shown to inhibit trigeminal ganglion (TGG) neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. Three clinical trials aimed at investigating the effectiveness of tonabersat as a preventive drug were negative, and conflicting results were obtained in other trials concerning its ability to relieve attacks. In contrast, in another clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks. Gap junction channels seem to be involved in several ways in the pathophysiology of migraine with aura and emerge as a new promising putative target in treatment of this disorder.

Resume L’obtention de distributions de dose d’intensite modulee se fait par planification inverse, ce qui necessite un algorithme d’inversion et une fonction objectif qui peut etre physique ou biologique ; les fonctions objectif biologiques ayant pour but de quantifier la probabilite de l’issue favorable du traitement. L’algorithme d’inversion analytique utilise se fonde sur l’analyse mathematique de la decomposition en valeurs singulieres et propose autant de solutions qu’il y a de faisceaux elementaires. A partir de la probabilite de controle tumoral, des probabilites de complications des tissus sains et de la probabilite de controle sans complications, trois fonctions d’evaluation biologiques des solutions sont definies et comparees par la difference des moindres carres entre les distributions de dose prescrite et obtenue. La configuration dˈirradiation utilisee est simplifiee : prescription de Brahme (modele bidimensionnel d’une irradiation pour cancer de la prostate) et neuf faisceaux (unidimensionnels). La determination par critere biologique de la solution optimale permet d’augmenter la dose moyenne dans la tumeur ainsi que son homogeneite par rapport a l’optimisation physique. A l’inverse, les organes a risque sont alors moins proteges. L’imposition de contraintes pertinentes permet alors d’obtenir des distributions de dose satisfaisantes. Certaines limitations apparaissent au niveau de la validite des modeles et des donnees utilises, ce qui pour l’instant nous semble exclure l’utilisation en routine clinique d’une optimisation uniquement biologique. La disponibilite future de nouvelles donnees biologiques permettra le developpement et notamment l’utilisation clinique de l’optimisation biologique.

Resume Objectif de l’etude. – Evaluer les consequences dosimetriques de la definition automatique de l’isodose de prescription basee sur la couverture de la lesion. Une serie de 124 malformations arterioveineuses a ete analysee. La qualite de ces planifications est quantifiee par l’ecart-type de l’histogramme dose–volume differentiel dans la lesion. Materiels et methodes. – Nous avons defini deux protocoles quantitatifs de definition automatique d’isodose de prescription a partir d’indices bases sur la couverture de la lesion en utilisant la definition volumique de la couverture (90 % du volume lesionnel), la definition basee sur les isodoses proposee par le Radiation Therapy Oncology Group (RTOG) (isodose de prescription egale a l’isodose minimale dans la lesion divisee par 0,9). Resultats. – Nous avons evalue les planifications obtenues pour ces deux protocoles en calculant differents indices dose–volume. Ces indices sont presentes en fonction de l’ecart-type de l’histogramme dose–volume differentiel dans la lesion afin de quantifier les consequences de leurs variations pour cette serie representative de planifications. La marge toleree par notre equipe est telle que la somme des facteurs de sous-dosage lesionnel et de surdosage des tissus sains reste inferieure a 1. Le protocole base sur la couverture volumique a donne des resultats situes dans cette marge. Celui utilisant la definition RTOG a genere des indices de conformation pouvant etre superieurs a 1. Conclusion. – La dose absolue doit etre decidee en tenant compte des indices dose–volume examines et des donnees cliniques. Un protocole de definition automatique d’isodose de prescription utilisant une couverture lesionnelle volumique semble plus judicieusement adapte aux planifications conformationnelles des malformations arterioveineuses en conditions stereotaxiques vues les variations observees au niveau du surdosage des tissus sains.

Resume Ces dernieres annees, la radiotherapie conformationnelle avec des faisceaux d'intensite uniforme a ete utilisee avec succes pour ameliorer la conformation de la distribution de dose dans le volume cible et dans les structures critiques. Cependant, plusieurs situations cliniques existent (volume cible complexe et structures critiques proches du volume cible) pour lesquelles cette technique ne peut pas fournir les distributions de dose souhaitees. De nouvelles techniques utilisant des faisceaux d'intensite modulee sont necessaires pour cela. La planification dosimetrique de ces faisceaux exige des systemes d'optimisation constitues de deux composantes: un algorithme d'inversion et un modele d'optimisation decrivant les criteres physiques ou biologiques a respecter. Nous presentons dans cet expose ces systemes d'optimisation en discutant chacune des deux composantes. Nous abordons le role des differents parametres d'irradiation tels que le nombre de faisceaux et l'energie des rayons X dans la procedure d'optimisation. Enfin, nous presentons quelques exemples realises par notre equipe.

Objectifs Les carcinomes palpebraux peuvent etre traites par irradiation ou chirurgie. L’irradiation peut etre delivree par electrons, iridium 192 ou photons de 50 kV. Les avantages de la radiotherapie de contact par photons de 50 kV sont la precision, le faible volume de traitement, la bonne protection des organes a risque, la simplicite et l’efficacite. Patients et methodes Entre juin 2010 et juin 2014, 38 patients ont recu une radiotherapie, par deux appareils (RT50 Philips ou PAPILLON50) delivrant un faisceau de photons de 50 kV, trois pour deux localisations synchrones. Ils etaient âges de 48 a 94 ans, 79 ans en moyenne. La tumeur etait situee sur la paupiere superieure pour 12 %, le canthus externe pour 7 %, la paupiere inferieure pour 22 %, le canthus interne pour 59 %. Il s’agissait d’un carcinome basocellulaire pour 76 %, un carcinome epidermoide pour 15 %, un melanome pour 6 %, un adenocarcinome sebace pour 3 %, de stade T1 pour 95 % et T2 pour 5 %. La radiotherapie etait exclusive et radicale pour 30 %, adjuvante pour 70 %, apres une resection R0 pour 38 % et R1 pour 62 %. Un tiers (34 %) des traitements a ete effectue pour des lesions en rechute de traitements anterieurs. Deux schemas principaux ont ete utilises : 42 Gy en six fractions de 7 Gy (traitements radicaux) et 35 Gy en 5 cinq fractions de 7 Gy. Resultats Le suivi median etait de 14 mois (2 a 45). Deux tumeurs (5 %) ont rechute, a 6 et 15 mois, et ont pu beneficier d’une chirurgie de rattrapage. Le taux de survie sans recidive etait de 89 %. La toxicite aigue etait a type d’erytheme de grade 1 pour 39 %, grade 2 pour 39 %, conjonctivite de grade 1 ou 2 pour 22 %, larmoiement de grade 1 pour 22 %, depilation ciliaire transitoire pour 100 %. La toxicite tardive etait a type de larmoiement de grade 1 pour 35 %, xerose oculaire de grade 1 pour 5 %, depilation ciliaire persistante pour 15 %, depigmentation pour 38 %. Une baisse d’acuite visuelle a ete constatee chez 5 % des patients, dont deux atteints anterieurement d’un glaucome ou d’une cataracte de l’œil traite. Conclusion La radiotherapie de contact de 50 kV des carcinomes palpebraux est efficace et bien supportee dans cette population selectionnee.

Irradiation of bone metastases primarily aims at alleviating pain, preventing fracture in the short term. The higher doses and more conformal dose distribution achievable while saving healthy tissue with new irradiation techniques have induced a paradigm shift in the management of bone metastases in a growing number of clinical situations.A search of the English and French literature was conducted using the keywords: bone metastases, radiotherapy, interventional radiology, vertebroplasty, radiofrequency, chemoembolization. RESULTS-DISCUSSION: Stereotactic irradiation yields pain relief rates greater than 90% in Phase I/II and retrospective studies. IMRT (static, rotational, helical) and stereotactic irradiation yield local control rates of 75-90% at 2 years. Some situations previously evaluated as palliative are currently treated more aggressively with optimized radiation sometimes combined modality interventional radiology.A recommendation can only be made for stereotactic irradiation in vertebral oligometastases or reirradiation. In the absence of a sufficient level of evidence, the increasing use of conformal irradiation techniques can only reflect the daily practice and the patient benefit while integrating economic logic care. The impact of these aggressive approaches on survival remains to be formally demonstrated by interventional prospective studies or observatories including quality of life items and minimal 2-year follow-up.

PURPOSE: To analyze doseevolume histogram parameters and pathologic response after preop- erative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). METHODS AND MATERIALS: From June 2007 to December 2011, 32 patients with a histolog- icallyproveninvasivecervicalcancerwithhighriskoflocalrecurrence(sizeO2 cm,adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39 Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. RESULTS: With a median clinical target volume of 50 cc (minimumemaximum, 42e74), the median V100 was 49 cc (minimumemaximum, 42e50). Median D90 was 45 Gy (equivalent dose at 2 Gy per fraction, 56 Gyab10). Median D2cc was 34 Gy, 31 Gy, 28 Gy, and 38 Gyab3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histo- logic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median fol- lowup of 24 months (minimumemaximum, 5e48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2eG3 toxicities were noticed. CONCLUSIONS: Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Doseevolume histogram parame- ters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs. 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.