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Summary Purpose The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. Materials and methods A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d’Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. Results Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA > 15 (77%) and/or Gleason 7 (4 + 3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. Conclusion To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

Resume Objectif L’objectif de cette etude est de presenter l’evolution de l’epidemiologie du cancer du rein dans l’Herault a partir des donnees collectees par le registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiels et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution du cancer du rein de 1987 a 2016. Nous avons analyse les donnees concernant l’incidence, la mortalite, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons compare ces resultats aux donnees nationales et internationales. Resultats Nous avons recense 3769 nouveaux cas de cancers du rein: 2628 chez l’homme (69,7 %) et 1141 chez la femme (30,3 %). En 2016, le cancer du rein etait le 8e cancer tous sexes confondus, le 7e cancer chez l’homme et le 11e chez la femme. Entre 1987 et 2016 le nombre de nouveaux cas de cancer du rein a ete multiplie par 4,2 chez l’homme et par 3,3 chez la femme. Le nombre de formes localisees a augmente de 9 % en 20 ans. En 2016 la probabilite, d’etre atteint d’un cancer du rein avant 75 ans est de 2,11 % pour un homme et de 0,62 % pour une femme. Conclusion En 30 ans, l’incidence du cancer du rein a fortement augmente dans l’Herault alors que l’on observe une diminution de sa mortalite. Ces donnees analytiques seront ameliorees par le developpement du Registre de l’Herault Specialise en Onco Urologie (RHESOU) Niveau de preuve 3.

To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer.Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (October 2011), and afterwards a mobile linac (50kV photons). The primary endpoint was the local recurrence rate (=ipsilateral breast cancer recurrences number). Secondary endpoints were recurrence-free survival (RFS), overall and specific survival, cosmetic results, and patient satisfaction.Of the present pre-planned analysis for the first 200 patients (median age: 68 years; range, 59-87 years) who received IORT between January 2010 and October 2014 (median follow-up of 53.4 months). A total of 193 patients were still alive. The local recurrence rate was 2.5% (n=5). The 1- and 5-year local RFS rates were 100% and 95.2%, respectively. At 12 months post-surgery, satisfaction about IORT was excellent for 86.9% of patients. Cosmetic results were considered by patients and physicians as good or very good in 89.4% and 97.3% of cases, respectively.IORT for selected patients with breast cancer shows low recurrence rates, good cosmetic outcomes and excellent satisfaction.

Background: Numerous studies have shown important impact of tumor-infiltrating lymphocytes (TILs) on natural or therapeutically-modified evolution of invasive breast cancer (IBC), however knowledge about TIL role in breast ductal carcinoma in situ (DCIS) is still limited. Because of the lack of reliable prognostic parameters, DCIS treatment is much less personalized than IBC therapy. BONBIS is a phase 3 French multicenter randomized trial designed to compare 2 schemes of adjuvant radiotherapy (adjRT) for DCIS (Azria et al, ASCO meeting 2011, TPS 131). It is accompanied by a translational study of DCIS pathobiology, aimed to discover predictive or prognostic biomarkers. Here we present results of TIL density (TIL-d) assessment, its correlation with pathobiology of the lesions and preliminary clues for further biomarker search in this DCIS cohort. Methods: Formalin-fixed, paraffin-embedded DCIS surgical specimens, obtained before adjRT, were prospectively collected and centrally reviewed for histology (architectural pattern, nuclear grade, proliferation, presence of necrosis), receptor status (ER, PR, HER2) and TIL-d. TIL-d was assessed on H&E-stained DCIS sections and reported as percentage of the DCIS specialized stroma area occupied by lymphocytes, lympho-plasmocytes and plasmocytes. Tumors were classified using the St Gallen 2011 criteria for IBC (PMID 21709140). For purpose of this study, the HER2+ category included all cases with HER2 protein expression scored 2+ and 3+, irrespective of the ERBB2 amplification status. Results: TIL-d was assessed in 495 cases, with distribution as follows: 0-4% TILs (D1): 85.5% (n=423); 5-9% TILs (D2): 9.3% (n=46); ≥10% TILs (D3): 5.2% (n=26). Molecular subclasses of those cases were: luminal A (LumA): 39% (n=192); luminal B (LumB): 25.5% (n=126), HER2+: 28.5% (n=141) and triple-negative (TN): 7% (n=33). TIL-d significantly correlated with molecular subclass: ≥5% TILs (D2) were found in 39.4% (13/33) TN, 22.7% (32/141) HER2+, 18.2% (23/126) LumB and only in 1% (2/192) LumA cases (p Citation Format: Bayol B, Tixier-Deves L, Dauplat M, Kwiatkowski F, Cayre A, Abrial C, Azria D, Penault-Llorca F, Radosevic-Robin N. Tumor-infiltrating lymphocytes in breast ductal carcinoma in situ: Correlations with tumor pathobiology in a French cohort of 495 cases (BONBIS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-03.

Objectifs La radiotherapie adjuvante (aRT) reduit le risque de rechute biochimique chez les patients atteints d’un cancer de la prostate traites par une prostatectomie radicale (RP). L’etude GETUG-AFU 17 a compare l’efficacite et la toxicite de l’aRT par rapport a la radiotherapie de rattrapage precoce (sRT), associee a un traitement hormonal. Methodes Cette etude multicentrique, de phase III, randomisee et controlee, a ete realisee dans 46 centres francais. Les patients devaient etre âges de plus de 18 ans, avec un statut Eastern Cooperative Oncology Group ≤ 1, une maladie classee pT3-4 et marges positives, pNx ou pN0, avec PSA postoperatoire ≤ 0,1 ng/mL. Les patients ont ete randomises (par minimisation ; 1 : 1) apres RP, entre aRT ou observation avec sRT, combine avec 6 mois de triptoreline. Le critere principal etait la survie sans evenement (EFS). Les criteres d’evaluation secondaires etaient la survie globale (SG), la survie sans metastase (MFS), l’incidence des toxicites aigues et tardives (CTCAE v3.0) et la qualite de vie (QoL) (echelles QLQ-C30 et PR-25). Cet essai est enregistre sous le numero ClinicalTrials.gov NCT00667069 . Resultats Entre le 7 mars 2008 et le 23 juin 2016, 424 patients ont ete inclus. Nous avions prevu d’inclure 718 patients. Les inclusions ont ete interrompues prematurement en raison de taux d’evenements etonnamment bas. Les caracteristiques initiales des patients et de leur tumeur etaient bien equilibrees entre les bras. Le suivi median etait de 75, 3 mois (IQR : 50–100). Lors de l’analyse, 115/212 patients (54 %) du bras sRT avaient commence le traitement. Avec 58 evenements, l’EFS a 5 ans etait de 92 % (IC95 % : 86–95) dans le bras aRT et de 90 % (IC95 % : 85–94) dans le bras sRT (HR = 0,81 [IC95 % : 0,48–1,36] ; test du log-rank p = 0,42). Le taux de SG a 5 ans etait de 96 % (IC95 % : 92–98) dans le bras aRT et de 99 % (IC95 % : 96–100) dans le bras sRT (HR = 1,60 [IC95 % : 0,71–3,60] ; p = 0,25). Les toxicites genito-urinaires de grade ≥ 2 etaient plus importantes dans le bras aRT (27 % vs 7 % ; p Conclusion L’etude GETUG-AFU 17 n’a montre aucun benefice en EFS pour l’aRT par rapport a la sRT. L’aRT a augmente le risque de toxicite genito-urinaire et de dysfonction erectile. Une strategie de sRT precoce pourrait epargner aux hommes la RT et la toxicite associee.

Introduction et but de l’etude Le traitement standard des recidives intraprostatiques isolees repose sur l’hormonotherapie. La prise en charge locale est discutee et souvent morbide. La reirradiation est une technique attrayante mais expose a un risque eleve de toxicite. La radiotherapie guidee par l’IRM permet d’obtenir des niveaux de doses eleves au niveau tumoral tout en diminuant les doses aux organes a risque. Le but de cette etude etait d’evaluer la toxicite aigue d’une reirradiation avec le systeme MRIdian® (ViewRay® Technologies, Inc.). Materiel et methodes Vingt patients pris en charge consecutivement a l’Institut du cancer de Montpellier (ICM) pour une recidive isolee intraprostatique prouvee d’un adenocarcinome de prostate entre le 21/10/2019 et le 13/03/2020 ont ete inclus. L’âge moyen des patients etait de 76 ans avec un indice de performance selon l’Organisation mondiale de la sante (OMS) de 0 ou 1. La concentration serique moyenne d’antigene specifique de la prostate avant la reirradiation etait de 6,45 μg/mL et l’International Prostate Symptom Score (IPSS) moyen de 8. L’intervalle moyen entre les deux irradiations etait de 9,9 ans. Quatre patients (soit 20 %) ont recu une hormonotherapie en concomitance. La radiotherapie etait adaptative pour sept patients (35 %). La dose prescrite etait de 30 Gy en cinq fractions pour 12 patients, 27,5 Gy en cinq fractions pour cinq patients, 30 Gy en six fractions pour deux patients et 38,7 Gy en neuf fractions pour un patient. Tous les patients ont ete revus en fin d’irradiation et 19 patients sur 20 a 6 semaines apres l’irradiation. Resultats et analyse statistique Les donnees de toxicite urinaire et rectale sont donnees dans le Tableau 1 . Seuls deux patients (10 %) ont vu une modification de l’IPSS entre le debut et la fin de l’irradiation avec un maximum de variation du score de 3 sur 35. Les profils de toxicite urinaire et digestive etaient semblables avant l’irradiation, en fin d’irradiation, et six semaines apres. Aucun patient n’a souffert de toxicite de grade superieur a 2. Pour tous les patients dont la concentration serique d’antigene specifique de la prostate a ete redosee six semaines apres la fin de l’irradiation (soit huit patients), une diminution a ete constatee avec une concentration moyenne avant l’irradiation de 5,95 μg/mL (extremes : 0,34–14,73 μg/mL) contre 3,63 (extremes : 0,08–13,09 μg/mL) a six semaines. Conclusion La reirradiation guidee par IRM des recidives intraprostatiques ne semble pas engendrer de toxicite aigue importante. Un recul plus important nous permettra d’evaluer la toxicite tardive et le benefice clinique.

Introduction et but de l’etude La radiotherapie adaptative guidee par IRM en conditions stereotaxiques est un traitement innovant pour l’irradiation des cancers du pancreas localement evolues. L’adaptation quotidienne du plan dosimetrique est obligatoire pour obtenir ces niveaux d’escalade de dose et garantir une protection suffisante des organes a risque. Le but de cette etude etait d’evaluer le benefice de traitements adaptes quotidiennement sur la couverture tumorale et les doses dans les organes a risque avec le MRIdian® (Viewray). Materiel et methodes Quinze patients traites consecutivement a l’Institut du cancer de Monpellier (ICM) pour un cancer du pancreas localement evolue entre le 20/10/2019 et le 27/03/2020 ont ete inclus. La dose prescrite etait de 50 Gy pour 12 patients, 40 Gy pour deux patients et 37 Gy pour un patient ; a chaque fois delivree fois en cinq fractions. Le volume tumoral macroscopique initial n’etait pas modifie sur les images journalieres, et 5 mm etaient ajoutes pour definir le volume cible previsionnel. Le volume cible previsionnel optimise etait defini comme le volume cible previsionnel moins les organes a risque plus 5 mm. Pour chaque fraction, un plan adaptatif etait genere apres recalage et redelineation de chaque organe a risque. La priorite etait donnee aux contraintes de doses dans les organes a risque et le plan etait valide en regardant la couverture au volume cible previsionnel optimise. Une comparaison a ete realisee entre les fractions predites (plan de base sur l’anatomie du jour) et les fractions delivrees (nouveau plan apres optimisation prenant en compte les nouveaux contours des organes a risque) en termes de couverture tumorale et de doses dans les organes a risque. Resultats et analyse statistique Le Tableau 1 presente les resultats dosimetriques pour differents niveaux de doses au niveau du volume cible previsionnel optimise, du volume tumoral macroscopique et des organes a risque digestifs, obtenus pour les fractions predites et les fractions delivrees (V95 % : volume recevant 95 % de la dose prescrite ; Dxcm3 : dose delivree dans x cm3). L’adaptation quotidienne apporte un benefice statistiquement significatif pour l’estomac, le duodenum, le jejunum et le volume cible previsionnel optimise. Sans adaptation les contraintes de doses maximales admises pour l’estomac, le duodenum et le jejunum seraient depassees. La priorite donnee a l’epargne des organes a risque ne compromet pas la couverture tumorale par rapport au plan previsionnel du jour (equivalence pour le volume tumoral macroscopique, benefice significatif pour le volume cible previsionnel optimise). Conclusion L’adaptation systematique du plan de traitement ameliore la qualite dosimetrique globale de la radiotherapie guidee par IRM en conditions stereotaxiques. Les benefices sont significatifs pour l’estomac, le duodenum, le jejunum et le volume cible previsionnel optimise.

Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.

Liver stereotactic body radiotherapy is a developing technique for the treatment of primary tumours and metastases. Its implementation is complex because of the particularities of the treated organ and the comorbidities of the patients. However, this technique is a treatment opportunity for patients otherwise in therapeutic impasse. The scientific evidence of liver stereotactic body radiotherapy has been considered by the French health authority as insufficient for its widespread use outside specialized and experienced centers, despite a growing and important number of retrospective and prospective studies, but few comparative data. This article focuses on the specific features of stereotactic body radiotherapy for liver treatments and the results of published studies of liver stereotactic body radiotherapy performed with classic linear accelerators and dedicated radiosurgery units., La radiothérapie stéréotaxique hépatique est une technique de traitement en développement pour le traitement des tumeurs primitives et secondaires. Sa mise en œuvre est complexe du fait des particularités de l’organe traité et des comorbidités des patients. Elle représente cependant une opportunité de traitement efficace pour beaucoup de patients en impasse thérapeutique. Son niveau de preuve est jugé insuffisant par la Haute Autorité de Santé (HAS) pour une large diffusion en dehors des centres expérimentés. Il existe pourtant un nombre conséquent et grandissant d’études rétrospectives ou prospectives, mais peu de données comparatives. Cet article résume les particularités de la radiothérapie stéréotaxique pour cette localisation et reprend les résultats des études publiées pour les machines dédiées et non dédiées.

The characterization of circulating tumor cells (CTCs) can lead to a promising strategy for monitoring residual or relapsing prostate cancer (PCa) after local therapy. The aim of this study was to compare three innovative technologies for CTC enumeration in 131 high-risk patients with PCa, before and after radiotherapy, combined with androgen deprivation. The CTC number was tested using the FDA-cleared CellSearch&reg, system, the dual fluoro-EPISPOT assay that only detects functional CTCs, and the in vivo CellCollector&reg, technology. The highest percentage of CTC-positive patients was detected with the CellCollector&reg, (48%) and dual fluoro-EPISPOT (42%) assays, while the CellSearch&reg, system presented the lowest rate (14%). Although the concordance among methods was only 23%, the cumulative positivity rate was 79%. A matched-pair analysis of the samples before, and after, treatment suggested a trend toward a decrease in CTC count after treatment with all methods. CTC tended to be positivity correlated with age for the fluoro-EPISPOT assay and with PSA level from the data of three assays. Combining different CTC assays improved CTC detection rates in patients with non-metastatic high-risk PCa before and after treatment. Our findings do not support the hypothesis that radiotherapy leads to cancer cell release in the circulation.

Resume Nous proposons dans cette revue de rapporter l’impact de la radiotherapie stereotaxique chez les patients ayant un cancer oligometastatique ou en oligoprogression en termes de survie sans progression metastatique et globale, et d’identifier quelle est la place de cette modalite de radiotherapie au sein du parcours–patient.

In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy.

The prognosis of infracentimetric breast cancers (BC) is heterogeneous. The EURISTIC survey describes how French oncology specialists perceive the prognosis of pT1a,b pN0 BCs. A self-administered questionnaire has been sent to over 2000 French BC specialists. Six hundred and sixty-three physicians responded. Fifty-eight percent do not consider tumor size as a key prognostic criterion. They consider that the cutoff for poor prognosis is 22mm, 10mm and 7mm for hormone receptors (HRs)+, HER2+ and triple-negative (TN) tumors respectively. Eighty-three percent of respondents consider that a HR+ pT1a,b tumor has a good prognosis (21% and 8% for HER2+ and TN respectively). Factors perceived as most detrimental are: HER2 overexpression (29% of respondents); HR- (20%); high grade (20%); TN status (14%); high KI67 (5%); presence of lymphovascular invasion (3%); young age (2%) and high mitotic index (1%). For French specialists, immunohistochemical characteristics, in particular hormone and HER2 status, are strong prognostic factors in BCs below 1cm.

International audience; ObjectifsL’objectif de cette étude est de présenter l’évolution de l’épidémiologie du cancer de la prostate dans l’Hérault à partir des données collectées par le registre des tumeurs de l’Hérault (RTH) sur une période de 30 ans.MéthodesÀ partir de la base de données du RTH, nous avons étudié l’évolution du cancer de la prostate de 1987 à 2016. Nous avons analysé les données concernant l’incidence, la mortalité, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons comparé ces résultats aux données nationales et internationales.RésultatsNous avons recensé 21 261 nouveaux cas de cancers de la prostate. Entre 1987 et 2016 le nombre de nouveaux cas de cancer de prostate a été multiplié par 2,8 avec un pic d’incidence en 2003. Le taux standardisé sur la population mondiale (TSM) de l’incidence est passé de 32,4 à 90,3 pour 100 000, la mortalité de 13,2 à 11,5 pour 100 000. Entre 2007 et 2015, le nombre cancer diagnostiqué au stade métastatique est passé de 5,1 % à 8,5 %, de même le taux de pT3 est passé de 17 % à 27,4 %. En 2016, la probabilité d’être atteint d’un cancer de prostate avant 75 ans est de 12,28 % (Fig. 1).ConclusionEn 30 ans, l’incidence du cancer de la prostate a fortement augmenté dans l’Hérault alors que l’on observe une diminution de sa mortalité. Ces données analytiques seront améliorées par le développement du Registre de l’Hérault Spécialisé en Onco-Urologie (RHESOU).

Purpose Radiation oncologists are responsible for deciding which day-to-day variations are acceptable or not in the treatment setup. However, properly qualified and trained radiation therapists might be capable to perform image registration. We evaluated in our centre the capability and accuracy of radiation therapists to validate positioning images in a prospective study. Methods and patients A total of 84 patients treated for prostate, head and neck, lung or breast cancer was prospectively and randomly included from July 2011 to July 2013 in radiotherapy unit of our institution. For each patient, three positioning images were randomly analysed. Two radiation oncologists analysed all positioning images and shifts decided by the radiation therapists in an independent and blinded way. The radiation oncologists had to decide whether to validate or not this shift and give a corresponding additional shift, if any. A theoretical disagreement rate less than 5% between radiation therapists and radiation oncologists was planned. Results A total of 240 images were analysed (head and neck: 15.0%; prostate: 14.2%; breast: 55.0%; lung: 15.8%). The global disagreement between radiation oncologists and radiation therapists for all the images analysed was 2.5% 95% confidence interval (95% CI) [1.0–5.0], corresponding to six images out of 240. A 100% agreement was reached for prostate and lung images, a 97.2% agreement for head and neck images and a 96.2% agreement for breast images. Conclusions The radiation therapist validation for repositioning images seemed accurate for image-guided radiotherapy in our institution. Periodic evaluation and in-house training are warranted when routine delegation of image registration to radiation therapists is considered.

Background To define a core set of geriatric data to be methodically collected in clinical cancer trials of older adults, enabling comparison across trials. Patients and methods Following a consensus approach, a panel of 14 geriatricians from oncology clinics identified seven domains of importance in geriatric assessment. Based on the international recommendations, geriatricians selected the mostly commonly used tools/items for geriatric assessment by domain (January–October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed according to RAND appropriateness ratings and feedback during three successive Delphi rounds (July–September 2016). The face validity of the G-CODE was assessed with two large panels of health professionals (55 national and 42 international experts) involved both in clinical practice and cancer trials (March–September 2017). Results and discussion After the last Delphi round, the tools/items proposed for the G-CODE were the following: (1) social assessment: living alone or support requested to stay at home; (2) functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3) mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6 months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini-Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity Index. More than 70% of national experts (42 from 20 cities) and international experts (31 from 13 countries) participated. National and international surveys showed good acceptability of the G-CODE. Specific points discussed included age-year cut-off, threshold of each tool/item and information about social support, but no additional item was proposed. Conclusion We achieved formal consensus on a set of geriatric data to be collected in cancer trials of older patients. The dissemination and prospective use of the G-CODE is needed to assess its utility.

Palliative radiation therapy is well-known in the setting of metastatic lesions (haemostatic, analgesic, anti-inflammatory aims, etc.). Palliative primary tumour radiotherapy is less studied. Here we propose a review of palliative indications of primary tumours, the most studied in the literature, and their radiotherapy modalities (target volumes and fractionation).

The ultimate goal in radiation oncology is to offer a personalized treatment to all patients indicated for radiotherapy. Radiomics is a tool that reinforces a deep analysis of tumors at the molecular aspect taking into account intrinsic susceptibility in a long-term follow-up. Radiomics allow qualitative and quantitative performance analyses with high throughput extraction of numeric radiologic data to obtain predictive or prognostic information from patients treated for cancer. A second approach is to define biological or constitutional that could change the practice. This technique included normal tissue individual susceptibility but also potential response of tumors under ionizing radiation treatment. These "omics" are biological and technical techniques leading to simultaneous novel identification and exploration a set of genes, lipids, proteins.

IF 11.855; International audience; BackgroundOutcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up.Patients and methodsInclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires.ResultsBetween November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76–1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66–1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51–1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and

Aim To evaluate the different techniques used for liver metastases Stereotactic Body Radiation Therapy (SBRT) planning. We especially focused on immobilization devices, motion management and imaging used for contouring. Background Although some guidelines exist, there is no consensus regarding the minimal requirements for liver SBRT treatments. Materials and methods We reviewed the main liver metastases SBRT publications and guidelines; and compared the techniques used for immobilization, motion management, margins and imaging. Results There is a wide variety of techniques used for immobilization, motion management and planning imaging. Conclusions We provide a subjective critical analysis of minimal requirements and ideal technique for liver SBRT planning.

Background In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU–RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. Patients and methods This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab–5-FU–RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU–RT before TME. Primary end point was pathological complete response (pCR) rate. Results Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). Conclusion Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab–Folfox-4 followed by bevacizumab–5-FU–RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. Clinical Trials.gov Identifier NCT 00865189.

Background To evaluate the relationship between MR measurements and the pathological tumor regression grade (pTRG). Methods Two radiologists independently reviewed the pre- and postchemoradiation therapy (CRT) rectal MR images of 73 consecutive patients with locally advanced low rectal cancer who underwent neoadjuvant CRT and subsequent surgery and measured tumor diameter, area, signal intensity (SI). The percentage reduction rate for each parameter was calculated. The absolute SI ratio reduction rate was defined as the absolute value of the SI ratio reduction rate. The Kruskal-Wallis test and multivariate analysis were performed to assess the correlation between each parameter and the pTRG. Receiver operating characteristic (ROC) curves were plotted for predicting favorable regression outcomes (pTRG 3–4). Results In multivariate analysis, the absolute SI ratio reduction rate was a significant predictor of pTRG for both radiologists. Area under the ROC curve (Az) values were 0.77–0.709 for diameter reduction rate, 0.757–0.694 for area, 0.652–0.648 for the SI ratio, 0.736–0.837 for the absolute SI ratio. Conclusion The absolute SI ratio reduction rate was significantly associated with pTRG and predicted favorable responses to CRT. Measurement of the diameter reduction rate is convenient and reliable in predicting favorable responses. J. Magn. Reson. Imaging 2015;42:421–426.

Resume Le traitement en un jour du cancer du sein se definit par l’association d’une chirurgie ambulatoire et d’une irradiation peroperatoire. La selection des patientes et des tumeurs associees a la rigueur du parcours patient assurent son succes. La technique operatoire n’est pas modifiee par l’irradiation peroperatoire. L’evaluation de l’indice de satisfaction des patientes est tres elevee. La moins value financiere actuelle de cette association therapeutique ne doit pas etre un frein a sa mise en place.

International audience; PURPOSE: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. METHODS AND MATERIALS: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. RESULTS: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. CONCLUSIONS: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.

Objectifs Des cohortes monocentriques ont suggere que le taux d’apoptose lymphocytaire radio-induit CD8 (RILA) peut predire les toxicites pelviennes (pt + ) tardives apres radiotherapie (RT) prostatique en intention curative. Nous avons evalue le role du RILA comme predicteur de pt + apres radiotherapie prostatique dans un essai prospectif multicentrique francais. Methodes Au total, 383 patients (pts) ont ete inclus dans 8 centres francais et traites par RT pour un cancer de prostate. Le RILA a ete realise en cytometrie de flux avant la RT. La RT a ete delivree en IMRT selon des volumes correspondant aux risques pronostiques (prostate + vesicules seminales 80 Gy ; prostate + pelvis 74 Gy ; loge prostatique 66 Gy). L’impact du RILA sur les toxicites pelviennes (objectif principal) ou sur les recidives a ete evalue en utilisant la methode des risques competitifs. Les analyses de type receiver-operator characteristic (ROC) ont ete realisees en intention de traiter. Cette etude a ete enregistree sur ClinicalTrials.gov ( NCT00893035 ). Resultats Au total, 352 ont recu la radiotherapie avec un tube de sang analysable. Au total, 222 (63 %), 83 (23,6 %) et 47 (13,4 %) pts ont recu respectivement une RT sur la prostate, la loge (prostatectomie) et le pelvis-prostate. Une hormonotherapie concomitante a ete administree chez 54 %. Avec un suivi median de 38 mois, les taux de toxicites tardives (grade 1–3) urinaires et digestives etaient respectivement de 22,7 % et de 11,7 %. L’incidence des pt + de grade ≥ 2 diminuait lorsque les pourcentages de RILA augmentaient (p = 0,03). Le risque de pt+ de grade ≥ 2 diminuait de moitie lorsque le RILA etait superieur a 24 %. Les symptomes urinaires initiaux pre-RT et une dose delivree a 50 % du rectum > 31 Gy augmentaient independamment le pt+. Le risque etait diminuee avec le RILA > 15 %. Conclusion Le RILA predit significativement le risque de pt+ associe a la presence de symptomes urinaires pre-therapeutiques et d’une dose rectale elevee. Cette etude valide l’utilisation du RILA dans un nomogramme multiparametrique en pratique clinique et permet de guider les praticiens et les patients dans la pertinence du choix entre prostatectomie et radiotherapie externe.

Background Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials. Patients and Methods Patients with mid/low magnetic resonance imaging–defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab–5-fluorouracil [5-FU]–radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU–RT then TME). Long-term efficacy and safety up to 5 years’ follow-up are reported. No comparison between arms was planned. Results Overall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years’ follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B. Conclusion Neoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab–5-FU–RT and TME in LARC. Bevacizumab–5-FU–RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged.

Background: Surrogate endpoints of overall survival (OS) are increasingly being used in cancer RCTs with the necessity of reducing randomized clinical trial (RCT) duration, cost and number of patients. However, most of these endpoints currently lack of standardized definition enabling a comparison of RCT results. The objective of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) initiative is to provide guidelines to standardize definitions of time-to-event endpoints in RCTs for different cancer sites. Some recommendations have been proposed for specific cancer sites but they do not rely on a formal consensus methodology. Here, we presented results for BREAST cancer. Methods: We relied on a validated formalized consensus process for the development of practice guidelines using a modified Delphi consensus method. International experts with various backgrounds and expertises were involved. First, the coordinating committee, a group of statisticians and epidemiologists involved in the design and conduct of RCTs, led a comprehensive literature review to identify time-to-event endpoints, events of interest and the existence of guidelines in metastatic and non metastatic settings. The steering committee, which included additional medical experts, validated the list and prepared the questionnaire sent for rating to an independent expert committee. Results: The consensus process involved 2 rounds of scoring (31 experts) and finally one in-person meeting. Each expert had to rate on a 1-9 scale if s/he agreed or not for including events (e.g. death from breast cancer) in the definition of time-to-event endpoints (e.g. progression-free survival). 150 events had to be scored for the 11 selected endpoints. Consensus was reached for 57% of the events after the 2 rounds of scoring. After the in-person meeting, consensus was reached for all the remaining events but one. Conclusions: The DATECAN guidelines should help standardizing definitions of commonly used endpoints. This process should (i) facilitate the comparison of RCTs and (ii) improve the quality of future RCTs by providing better estimation of sample size and treatment effect by disseminating the recommendations in major congress. (previously presented to ASCO’13) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-17-02.

Introduction The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. Methods Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. Results Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. Conclusion From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined.

Resume Objectif Le but du Comite de cancerologie de lʼAssociation francaise dʼurologie etait de proposer une mise a jour des recommandations dans la prise en charge du cancer de la prostate (CaP). Methodes Une revue systematique (Medline) de la litterature de 2013 a 2016 a ete conduite par le CCAFU concernant les elements du diagnostic, les options de traitement et la surveillance du CaP, en evaluant les references avec leur niveau de preuve. Resultats Les recommandations precisent la genetique, lʼepidemiologie et les moyens diagnostiques du CaP. Lʼimagerie par resonance magnetique (IRM) est lʼexamen dʼimagerie de reference du cancer localise. Le score de Gleason a ete redefini par lʼInternational Society of Urological Pathology (ISUP) en cinq groupes pronostiques. Les moyens therapeutiques ont ete detailles, puis recommandes en fonction des situations cliniques. La surveillance active (SA) est une option therapeutique de reference pour les tumeurs de faible risque evolutif. La chirurgie reste une solution therapeutique majeure du CaP localise. Elle doit etre envisagee dans un cadre multimodal pour les formes a haut risque. La radiotherapie doit utiliser une technique conformationnelle tridimensionnelle si possible en modulation dʼintensite a une dose > 76 Gy. Lʼhypofractionnement modere apporte un controle biochimique equivalent sans augmentation majeure de la toxicite. LʼHT courte peut etre associee a lʼirradiation pour les tumeurs de risque intermediaire « fort ». Pour les formes a haut risque, lʼassociation a une HT longue reste la reference. LʼHT est le traitement de fond au stade metastatique. La prevention des effets secondaires de lʼHT est fondamentale. Lʼhormonochimiotherapie de premiere ligne pour le traitement des CaP metastatiques hormono- et chimio-naifs est le traitement standard en cas de cancer dʼemblee metastatique chez les patients dont lʼetat de sante est compatible avec lʼusage de docetaxel. Chez les patients presentant un cancer de prostate resistant a la castration (CPRC), lʼapport des nouvelles therapies qui ont emerge ces dernieres annees aide a mieux controler la progression tumorale et a ameliorer la survie. Conclusions Cette actualisation des recommandations francaises doit contribuer a ameliorer la prise en charge des patients porteurs dʼun CaP. © 2016 Elsevier Masson SAS. Tous droits reserves.

International audience; OBJECTIVE:The purpose of the guidelines national committee CCAFU on bladder cancer was to propose updated french guidelines for non-muscle invasive (NMIBC) and invasive (MIBC) bladder cancers.METHODS:A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence.RESULTS:Diagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment : instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan; MRI and FDG-PET remain optional. Cystectomy associated with extensive pelvic lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples. The interest of neoadjuvant chemotherapy is well known for all MIBC, wathever the stage. Thus, neoadjuvant chemotherapy is recommended for all eligible patients according PS (PS 60ml/mn). As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC). In second line treatment, only chemotherapy using vinflunine has been validated to date, even if results of immunotherapy clinical trials are encouraging.CONCLUSION:These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for NMIBC and MIBC. © 2016 Elsevier Masson SAS. All rights reserved.

International audience; Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

International audience; Penile cancer is a rare entity with only 2000 new cases a year in the United States. Even though early stage penile cancer has an excellent prognosis, patients with positive pelvic lymph nodes have an overall 5-year survival rate under 10%. There is no consensus for the management of pelvic node-positive patients, although most guidelines are in favour of pelvic lymph node dissection for patients with two or more positive nodes, followed by adjuvant chemotherapy. We describe here the case of a patient with numerous metastatic lymph nodes at diagnosis, treated with chemoradiation (66Gy with concurrent gemcitabine) after failure of first-line chemotherapy and still alive and disease-free 7 years after diagnosis.

IEEE Conference on Standards for Communications and Networking, CSCN 2015 -- 28 October 2015 through 30 October 2015 -- 119154 Purpose: In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. Materials and methods: 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. Results: Mean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. Conclusions: In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.

Resume Durant le dernier congres de la Societe francaise de radiotherapie oncologique (SFRO), un point a ete fait sur les differentes strategies therapeutiques proposees dans la prise en charge des metastases cerebrales. Les indications et les limites de la chirurgie, de la radiotherapie stereotaxique et de la radiotherapie panencephalique, ainsi que leurs benefices en termes de survie, de controle intracerebral et d’amelioration du statut fonctionnel et neurocognitif ont ete discutes. L’influence des differents phenotypes de cancer du sein sur la survenue de metastases cerebrales ainsi que leurs impacts sur le traitement des metastases cerebrales ont egalement ete evoques. Ainsi, la chirurgie ameliore la probabilite de survie globale des patients atteints d’une metastase cerebrale solitaire et est particulierement indiquee chez le patient symptomatique. La radiotherapie stereotaxique a une efficacite comparable a la chirurgie en termes de survie. Ces traitements sont principalement indiques pour les patients en bon etat general, atteints d’une a trois metastases cerebrales de diametre de moins de 3 cm d’une tumeur controlee en dehors du cerveau. La radiotherapie panencephalique apres traitement local des metastases cerebrales est controversee en raison de sa toxicite cognitive tardive. Des techniques permettant d’epargner la region hippocampique sont en cours d’investigation afin de diminuer cette toxicite. En ce qui concerne les metastases cerebrales d’origine mammaire, leur risque de survenue est augmente chez les patientes atteintes de tumeur « triple negative » et celles exprimant HER2. Le pronostic differe aussi selon le sous-groupe biologique, avec un allongement de la survie constate chez les patientes atteintes de tumeur exprimant HER2 traitees par des agents ciblant le recepteur HER2. Les associations optimales des traitements systemiques et locaux restent cependant a definir.

Background and purpose: Postoperative whole breast external radiotherapy remains the current standard of care for patients with early operable breast cancer. In the elderly, the low crude numbers of recurrence and the frequency of comorbidities urged teams to investigate the feasibility and the results of intraoperative radiotherapy (IORT) delivered in one fraction during the surgical procedure. Material and methods: 94 patients (> 65 years old) accepted to be included in this phase II trial according to clinical and histopathology criteria and signed the informed consent. Among them, 42 presented all the inclusion criteria, namely pT0-1 pN0, non lobular invasive unifocal carcinoma, margin ≥ 2 mm (assessed during the surgical procedure) and estrogen receptors positivity. All patients were operated upon in a dedicated IORT facility (linear accelerator) located centrally among six operated rooms. After tumor removal, the surgical bed was approximated by sutures to bring the tissue within the radiation target volume. The tumor beds were completely encompassed by 4 to 6 cm circular fields using flattened applicators at a 110 cm distance. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electron with energies ranging from 6 to 10 MeV. In vivo dosimetry was performed for all patients using real-time in vivo semiconductor detectors (PTW) fixed by the surgeon within the surgical bed. A 5 year adjuvant hormonotherapy was prescribed according to the recommendations. Primary end-point was the quality index [QI] - ratio between the prescribed dose and the in vivo measured dose-. Secondary endpoints corresponded to quality of life, local recurrences, cosmetic results, specific and overall survival. Results: Median follow-up is now 54 months [range 12–62]. Median age was 72 years [66-80] and median tumor diameter was 10 mm [3-19 mm]. 36 tumors were grade 1 or 2 and 100 % of the tumors expresses estrogen receptors. All patients received the total prescribed dose. No external postoperative radiotherapy was delivered. Intraoperative dosimetry demonstrated a good accordance between the delivered and the prescribed doses for 97% of the 37 evaluable patients. No acute grade 2 or greater toxicities were observed. Scores for quality of life were collected for all patients and showed no modification between pre and posttreatment evaluations. Late cosmetic result was good to excellent. All patients are still alive and the 4 year-disease-free-survival is currently 97%. Two patients recurred: (i) one infracentimetric superficial recurrence in the border of the surgical bed and close to the skin (at 18 months) (ii) a second primary tumor in another quadrant (at 6 months). These two patients underwent salvage mastectomy and are free of disease at the time of analysis. Conclusion: For a very selected population, these results confirm that partial breast IORT with electrons may be considered as an interesting alternative to the standard 6-weeks radiotherapy, offering therefore a safe one-step procedure treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-12.

Introduction: Incidence of brain metastases (BM) from breast cancer has increased over the past decade, especially for HER2(+) tumours. Several scores and prognosis systems have been developed in the brain metastases (BM) setting in order to help physicians tailor treatment options depending on patient prognosis and to stratify patients enrolled in clinical studies. The aim of our study was to compare the clinical relevance of the major classifications and existing prognostic scores in a population of breast cancer patients affected by BM. Methods and Materials: In this retrospective study conducted in Montpellier and Nice Cancer Centres, we retrospectively reviewed the clinical and biological data of 250 patients diagnosed with breast cancer BM between 1995 and 2010. Prognostic value and accuracy of recursive partitioning analysis (RPA), graded prognostic assessment (GPA), basic score for brain metastases (BS-BM) and a clinico-biological score (BS) developed in phase I study and validated in the BM setting were compared. Results: Median age at BM diagnosis was 55 years-old. Most patients (74%) had good performance status (0-1). Brain was the first metastatic site in one third of patients (33.6%). In 12.4% of cases, no extracerebral metastases were detected at BM diagnosis. Among the 250 patients’ tumors, 43.6% overexpressed HER2 receptor and 25.6% were triple negative (negative estrogen receptor, progesterone receptor and HER2 status). After a median follow up of 4.5 years, median overall survival from BM diagnosis was 8.9 months (CI 95%, 6.9−10.3 months). The four scores were able to discriminate patients according to their survival. Chi2 tests showed a correlation between the different scoring systems. In multivariate analysis, the elimination model identified RPA (p = 0.031; hazard ratio, 0.77; 95% confidence interval, 0.64−0.91) and BS (p = 0.043; hazard ratio, 0.5; 95% confidence interval, 0.31−0.80) as the only two independent predictors of survival. RPA was the most accurate score in order to identify patients with high life expectancy, while RPA and BS were the most accurate scores to classify patients with short life expectancy. Conclusions: In a general unselected population of breast cancer affected by BM, RPA seems to be the most useful score. Integration of biological parameters in addition of existing clinico-radiological scores is promising in order to improve the prognostic determination accuracy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-09.

Background Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial “BONBIS” is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. Methods: A total of 1950 patients DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractions vs. (B) WB radiotherapy of 50 Gy in 25 fractions plus a localized 16-Gy boost in 8 fractions. The primary endpoint is local-relapse free survival (LRFS). This trial is designed to detect an expected rate in control arm of 7% and 4 % in experimental arm. With 90% power and a=0.05, 137 events are necessary to achieve the main goal. An interim analysis is planned after 50% of observed event. Stratifications are made based on recognized prognostic factors: age, hormonal treatment, differentiation, circumstance of diagnosis, surgical margin, centre. Secondary endpoints are relapse free survival, overall survival, acute and late toxicities, cosmetic results, and quality of life. Translational researches are also planned to identify intrinsic radiosensitivity of normal tissues (radiation-induced apoptosis assay, genome-wide association study) but also predictive models of tumor recurrences. Inclusions have started in November 2008 and are not so far than the planned estimation. This trial is granted by the French National Cancer Institute (PHRC 2008) and supported by the French National Society of Radiation Oncology (SFRO). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-06-01.

summary Background & aims: To assess the efficacy on acute grade 3 or 4 oral mucositis of immune modulating formulae during radiochemotherapy in head and neck neoplasms. Methods: Prospective phase II trial. 40 patients without malnutrition were assigned to receive radiotherapy (66 Gy; 6.5 weeks) combined with cisplatin (D 1, 22 and 43). Patients received an oral supplementation (1 l/day, formula enriched with L-arginine, u-3 fatty acids, and ribonucleic acids) for 5 days before each cycle of chemotherapy. Results: Twenty one (52.5%) patients showed at least one NCI grade 3 or 4 toxicity. Only 5 patients (12.5%) had a grade 3 or 4 NCI oral mucositis. The rate of severe mucositis was 6.8% when compliance with the oral dietary regimen was greater than 75% and 27.3% when compliance with the specialised regimen was less than 75% (P ¼ 0.082). Conclusions: Oral supplementation with an immune modulating formula could reduce severe acute oral mucositis.