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In stage IV cancers, locoregional management of primitive tumours as surgery and/or radiotherapy improved both progression-free survival and overall survival. Among metastatic cancer patients, some of them are considered as oligometastatic stage as they present few metastatic sites associated with low tumor aggressiveness. For those patients, metastatic local control, and therefore prolonged time to progression should be reached through local treatments as surgery and/or radiofrequency ablation and/or stereotactic radiotherapy. Here we propose a review of oligometastatic stage and results from extracranial stereotactic radiotherapy in terms of efficacy and tolerance. [ABSTRACT FROM AUTHOR]

Background The kinesin spindle protein Eg5 is involved in mitosis, and its inhibition promotes mitotic arrest. EMD 534085, a potent, reversible Eg5 inhibitor, demonstrated significant preclinical antitumor activity. Methods This first-in-man, single-center, open-label, phase I dose-escalation study (3 + 3 design) investigated EMD 534085 safety, pharmacokinetics and antitumor activity in refractory solid tumors, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. EMD 534085 (starting dose 2 mg/m/day) was administered intravenously every 3 weeks. Doses were escalated in 100 % steps in successive cohorts of 3 patients until grade 2 toxicity occurred, followed by 50 % until the first dose-limiting toxicity (DLT) arose. If <2 of 6 patients experienced a DLT, doses were further increased by 25 %. Dose-escalation was stopped if a DLT occurred in ≥2 of 6 patients. Results Forty-four patients received EMD 534085. Median treatment duration was 43 days (range, 21-337). Thirty-eight patients (86 %) received ≥2 cycles. DLTs were grade 4 neutropenia (1 patient each at 108 and 135 mg/m/day), and grade 3 acute coronary syndrome with troponin I elevation (1 patient at 135 mg/m/day). The maximum tolerated dose (MTD) was 108 mg/m/day. The most common treatment-related adverse events were asthenia (50 %) and neutropenia (32 %). EMD 534085 appeared to have linear pharmacokinetics. Increase in phospho-histone H3 positive cells in paired pre- and on-treatment biopsies showed evidence of target modulation. No complete or partial responses were observed. Best response was stable disease in 23 patients (52 %). Conclusions EMD 534085 appeared to be well tolerated; MTD was 108 mg/m/day. Preliminary antitumor results suggested limited activity in monotherapy. [ABSTRACT FROM AUTHOR]

J. Cyrta, F. Andreiuolo, S. Azoulay, C. Balleyguier, C. Bourgier, C. Mazouni, M.-C. Mathieu, S. Delaloge and P. Vielh Pure and mixed mucinous carcinoma of the breast: fine needle aspiration cytology findings and review of the literature Objective: Mucinous (colloid) breast carcinoma accounts for 1-6% of all breast cancer. It comprises pure mucinous tumours and mixed infiltrating ductal carcinomas with a mucinous component. As this latter mixed form has a worse prognosis than pure colloid carcinoma, making this diagnosis on fine needle aspiration cytology (FNAC) might influence the choice of treatment. Methods: We report a consecutive series of 22 cases consisting of 17 mixed and five pure mucinous carcinomas diagnosed by cytology and verified on histopathology. Patients underwent FNAC at the one-stop clinic of our institution during a 7-year period of time. Cytological findings were evaluated by a semi-quantitative method and included percentage of smear surface occupied by mucin, shape of cell groupings, size and outline of tumour nuclei as well as presence or absence of nucleolus. Results: Three of five pure mucinous carcinomas displayed at least two of the following features: abundant mucin, small nuclei and/or regular nuclear outlines. Sparse mucin, large nuclei, irregular nuclear outlines or the presence of nucleoli were found in 7 out of 17 mixed mucinous carcinomas but not in pure tumours. Conclusion: Cytopathological identification of patients with pure mucinous carcinomas may be performed in a limited number of cases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. Methods: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. Results: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. Conclusions: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To actualize and to detail guidelines used in technical radiotherapy and indications for innovative radiation technologies in early axillary node negative breast cancer (BC). Methods: Dosimetric and treatment planning studies, phase II and III trials, systematic reviews and retrospective studies were all searched (Medline® database). Their quality and clinical relevance were also checked against validated checklists. A level of evidence was associated for each result. Results: A total of 75 references were included. Adjuvant BC radiotherapy (50Gy/25 fractions/5 weeks followed by a tumor boost of 16Gy/8 fractions) is still the standard of care. Overall treatment time could be shortened for patients who present with low local relapse risk BC by using either hypofractionated whole breast irradiation; or accelerated partial breast irradiation. BC IMRT is not used in current practice. Conclusion: Our group aimed to provide guidelines for technical and clinical applications of innovative BC radiation technologies. [Copyright &y& Elsevier]

Abstract: Breast cancer treatment guidelines are based on usual prognostic factors such as size, histological grade, axillar lymph node involvement, expression of hormonal receptors. The intrinsic molecular classification is giving additional information over clinical and pathological features. Predictive models for systemic relapse have been established and are currently under clinical investigation to determine precisely when chemotherapy is needed. This review will look after the implications of this classification in terms of radiobiology: on one hand, we will look if this classification helps for loco-regional relapse prediction and on the other hand, if it is able to change the radiotherapy schedule within the molecular classification. [Copyright &y& Elsevier]

Abstract: After normal tissue exposure to radiation therapy, late side effects can occur and may reduce patients’ quality of life due to their progressive nature. Late toxicities occurrence is the main limiting factor of radiotherapy. Various biological disorders related to irradiation are involved in the development of late toxicities including fibrosis. The present review will focus on the recent physiopathological and molecular mechanisms described to be involved in the development of late radio-induced toxicities, that provide therapeutic perspective for pharmacomodulation. [Copyright &y& Elsevier]

Abstract: Purpose: Since 2009, accelerated partial breast irradiation (APBI) in North America has been allowed to be used for selected group of patients outside a clinical trial according to the ASTRO consensus statement. In France, accelerated partial breast irradiation is still considered investigational, several clinical trials have been conducted using either intraoperative (Montpellier) or Mammosite® (Lille) or brachytherapy modality (PAC GERICO/FNCLCC). Here, we report the original dosimetric results of this technique. Patients and methods: Since October 2007, Institut Gustave-Roussy has initiated a phase II trial using 3D-conformal accelerated partial breast irradiation (40Gy in 10 fractions BID in 1week). Twenty-five patients with pT1N0 breast cancer were enrolled and were treated by two minitangent photons beams (6MV) and an “en face” electron beam (6–22MeV). Results: The mean clinical target volume and planning target volume were respectively 15.1cm3 (range: 5.2–28.7cm3) and 117cm3 (range: 52–185cm3). The planning target volume coverage was adequate with at least a mean of 99% of the volume encompassed by the isodose 40Gy. The mean dose to the planning target volume was 41.8Gy (range: 41–42.4Gy). Dose inhomogeneity did not exceed 5%. Mean doses to the ipsilateral lung and heart were 1.6Gy (range: 1.0–2.3Gy) and 1.2Gy (range: 1.0–1.6Gy), respectively. Conclusion: The 3D conformal accelerated partial breast irradiation using two minitangent and “en face” electron beams using a total dose of 40Gy in 10 fractions BID over 5days achieves appropriate planning target volume coverage and offers significant normal-tissue sparing (heart, lung). Longer follow-up is needed to evaluate the tissue tolerance to this radiation dose. [ABSTRACT FROM AUTHOR]

Abstract: Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform reirradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models. [ABSTRACT FROM AUTHOR]

Le concept de médecine personnalisée s’est fortement développé dans la prise en charge des cancers du sein ces dernières années. Il repose sur des tests biologiques complexes, sur la tumeur évaluant le pronostic et la sensibilité de la maladie aux traitements potentiels. La génétique constitutionnelle est aujourd’hui capable d’apporter des informations essentielles et complémentaires aux données somatiques, en matière de pronostic local et général, mais surtout en termes de risque de nouveau cancer. Dans les années qui viennent, elle sera essentielle pour l’évaluation de la sensibilité potentielle spécifique aux thérapeutiques, en particulier avec l’arrivée de thérapeutiques ciblées spécialisées (les inhibiteurs de poly[ADP-ribose] polymérase [PARP] étant les chefs de file en cas d’anomalies constitutionnelles de réparation de l’ADN par exemple). Dans certains cas très rares, la sensibilité thérapeutique peut être excessive, comme en cas de présence d’une anomalie constitutionnelle de type p53 qui peut contre-indiquer les radiations ionisantes. Cette revue fait le bilan de nos connaissances en matière d’impact de la génétique constitutionnelle dans la prise en charge personnalisée des cancers du sein en 2010 et les modifications attendues dans les années à venir. [ABSTRACT FROM AUTHOR]

En situation adjuvante, la radiothérapie (RT) de la glande mammaire en totalité est le gold standard après chirurgie conservatrice. Le contrôle de qualité est requis à toutes les étapes de la procédure. La technique d’irradiation mammaire (± les aires ganglionnaires) est relativement bien standardisée, et l’apport du scanner dans la définition des volumes et l’optimisation des traitements est une avancée considérable de la RT conformationnelle en 3D. Devant le développement technologique, la question de l’utilisation de la modulation d’intensité et de la haute technicité pour améliorer encore plus le ratio bénéfice/risque est posée. Actuellement, les règles de bonnes pratiques, en termes d’indications, de fréquence d’utilisation et de contrôle de qualité de ces techniques innovantes restent à définir pour de nombreux types de cancers, y compris le cancer du sein. La faisabilité est démontrée pour la majorité des nouvelles techniques dans des séries limitées de patientes atteintes de cancer du sein, il reste à démontrer leur impact sur la réduction des toxicités à distance, l’amélioration de la survie et la détermination des patientes qui en bénéficieront le plus dans un contexte de traitements et d’associations thérapeutiques de plus en plus innovants. [ABSTRACT FROM AUTHOR]

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Background: Late radiation enteritis in humans is associated with accumulation of extracellular matrix and increased connective tissue growth factor (CTGF) expression that may involve intestinal muscular layers. Aims: We investigated the molecular pathways involved in maintenance of radiation induced fibrosis by gene profiling and postulated that alteration of the Rho pathway could be associated with radiation induced fibrogenic signals and CTGF sustained expression. Patients and methods: lleal biopsies from individuals with and without radiation enteritis were analysed by cDNA array, and primary cultures of intestinal smooth muscle cells were established. Then, the effect of pharmacological inhibition of p160 Rho kinase, using Y-27632, was studied by real time reverse transcription-polymerase chain reaction, western blot, and electrophoretic mobility shift assay. Results: Molecular profile analysis of late radiation enteritis showed alterations in expression of genes coding for the Rho proteins. To investigate further the involvement of the Rho pathway in intestinal radiation induced fibrosis, primary intestinal smooth muscle cells were isolated from radiation enteritis. They retained their fibrogenic differentiation in vitro, exhibited a typical cytoskeletal network, a high constitutive CTGF level, increased collagen secretory capacity, and altered expression of genes coding for the Rho family. Rho kinase blockade induced a simultaneous decrease in the number of actin stress fibres, α smooth muscle actin, and heat shock protein 27 levels. It also decreased CTGF levels, probably through nuclear factor KB inhibition, and caused decreased expression of the type I collagen gene. Conclusion: This study is the first showing involvement of the Rho/Rho kinase pathway in radiation fibrosis and intestinal smooth muscle cell fibrogenic differentiation. It suggests that specific inhibition of Rho kinase may be a promising approach for the development of antifibrotic therapies. [ABSTRACT FROM AUTHOR]