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Background: Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis., Materials and Methods: 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV&#95;crop (reference), cropped 5 mm from the skin and ii) CTV&#95;skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso 95% ) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas&#95;skin/Atlas&#95;crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression., Results: There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV&#95;skin and Atlas&#95;skin contours had lower NTCP estimates (-3.92%, IQR 4.00, p < 0.05) compared to CTV&#95;crop. No significant difference was observed for Atlas&#95;crop and Iso 95% contours compared to CTV&#95;crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from "skin" contours showed higher agreement with observed events., Conclusion: Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (OR GeneralFatigue  = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background and Purpose: Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy., Materials and Methods: A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure., Results: Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10 -5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10 -8 ), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10 -10 ), rs75912034 (p = 1.12 × 10 -10 ), rs145328458 (p = 1.06 × 10 -9 ) and rs61966612 (p = 1.23 × 10 -9 ), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10 -8 ) and rs34063419 (p = 1.21 × 10 -8 ), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10 -8 ). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level., Conclusions: This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Adjuvant radiotherapy is one of the major anticancer treatments in early breast cancer patients. Acute and late radio-induced effects may occur during or after breast cancer radiotherapy, and their medical management is a major issue for radiation oncologists. Here, the present review of literature embraces complementary non-pharmacological interventions, which could be combined to adjuvant radiotherapy in order to improve patients care., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS)., Materials and Methods: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients., Results: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities., Conclusions: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer., Methods and Materials: 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 (

We propose in this short review to report the impact of stereotactic body radiation therapy (SBRT) in oligometastatic or oligoprogressive cancer patients in terms of metastatic progression-free and global survival, and to identify the place of SBRT in patient's pathway., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data., Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated., Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung)., Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers., Patient Summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Biomarkers for predicting late normal tissue toxicity to radiotherapy are necessary to personalize treatments and to optimize clinical benefit. Many radiogenomic studies have been published on this topic. Conversely, proteomics approaches are not much developed, despite their advantages., Methods: We used the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach to analyze differences in protein expression levels in ex-vivo irradiated (8 Gy) T lymphocytes from patients with grade ≥ 2 radiation-induced breast fibrosis (grade ≥ 2 bf+) and patients with grade < 2 bf + after curative intent radiotherapy. Patients were selected from two prospective clinical trials (COHORT and PHRC 2005) and were used as discovery and confirmation cohorts., Results: Among the 1979 quantified proteins, 23 fulfilled our stringent biological criteria. Immunoblotting analysis of four of these candidate proteins (adenylate kinase 2, AK2; annexin A1; heat shock cognate 71 kDa protein; and isocitrate dehydrogenase 2) confirmed AK2 overexpression in 8 Gy-irradiated T lymphocytes from patients with grade ≥ 2 bf + compared with patients with grade < 2 bf+. As these candidate proteins are involved in oxidative stress regulation, we also evaluated radiation-induced reactive oxygen species (ROS) production in peripheral blood mononuclear cells from patients with grade ≥ 2 bf + and grade < 2 bf+. Total ROS level, and especially superoxide anion level, increased upon ex-vivo 8 Gy-irradiation in all patients. Analysis of NADPH oxidases (NOXs), a major source of superoxide ion in the cell, showed a significant increase of NOX4 mRNA and protein levels after irradiation in both patient groups. Conversely, only NOX4 mRNA level was significantly different between groups (grade ≥ 2 bf + and grade < 2 bf+)., Conclusion: These findings identify AK2 as a potential radiosensitivity candidate biomarker. Overall, our proteomic approach highlights the important role of oxidative stress in late radiation-induced toxicity, and paves the way for additional studies on NOXs and superoxide ion metabolism.

This review discusses the clinical applications of magnetic resonance imaging (MRI) for the assessment of neo-adjuvant chemotherapy (NAC) indication, axillary lymph node status, preNAC cancer prognosis, early and intermediate response to NAC, and post-NAC residual disease in patients with breast cancer. Contrast-enhanced MRI with analysis of the tumor morphological features and qualitative enhancement kinetics must be considered as the standard method for pre-NAC breast cancer staging and post-NAC residual disease assessment. Diffusion-weighted imaging (DWI) is easy to perform and may increase the specificity of breast MRI for tumor staging, and also for the assessment of tumor multifocality and multicentricity and lymph node status. It also provides an ancillary added value in the early and post-NAC response evaluation. Changes in the functional tumor volume are the main criterion for the early response analysis. Other MRI methods, such as quantitative perfusion analysis, MR spectroscopy and texture analysis, are still under study., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Standard of care in breast cancer management is well-defined. However, some gray zones still exist, in particular adjuvant radiotherapy indications in case of pN1mi breast cancer. Here we propose to define their prognosis, to underpin the benefit of adjuvant treatments in such patients' management and to define lymphedema risk, which is the most common late side effect of locoregional treatments., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium., Materials and Methods: The analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity., Results: For all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance., Conclusion: This study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Breast cancer remains a potentially lethal disease, which requires aggressive treatments and is associated with long-term consequences. Its prognosis is linked to both tumor biology and burden at diagnosis. Although treatments have allowed important improvements in prognosis over the past 20 years, breast cancer screening remains necessary. Mammographic screening allows earlier stage diagnoses and a decrease of breast cancer specific mortality. However, breast cancer screening modalities should be revised with the objective to address demonstrated limitations of mammographic screening (limited benefit, imperfect sensitivity and specificity, overdiagnoses, radiation-induced morbidity). Furthermore, both objective and perceived performances of screening procedures should be improved. Numerous large international efforts are ongoing, leading to scientific progresses that should have rapid clinical implications in this area. Among them is improvement of imaging techniques performance, development of real time diagnosis, and development of new non radiological screening techniques such as the search for circulating tumor DNA, development of biomarkers able to allow precise risk evaluation and stratified screening. As well, overtreatment is currently addressed by biomarker-based de-escalation clinical trials. These advances need to be associated with strong societal support, as well as major paradigm changes regarding the way health and cancer prevention is perceived by individuals., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2016. Published by Elsevier SAS.)

Background: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs)., Patients and Methods: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat., Results: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared with those who developed grade ≤1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10(-9)) and rs1182532 (P = 3.6 × 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33., Conclusions: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF., Registered Clinical Trial: NCT00208273., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA provide better plan considering low doses to healthy brain even if quality indexes are better for the others techniques. For multiple lesions, RANC seems to be the best compromise, due to the ability to deliver a good conformity and homogeneity plan while sparing healthy brain tissue. For a single lesion close to organs at risk, RAT is the most appropriate technique.

Objectives: To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations., Patients and Methods: A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis., Results: The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting., Conclusion: This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial., Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here., Findings: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥ 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ≥ 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ≥ 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥ 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade ≥ 2 bf + was equal to 91% for RILA ≥ 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade ≥ 2 bf + was estimated at 14%. A significant decrease in the risk of grade ≥ 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA ≥ 12% (sHR = 0.45, p = 0.002)., Interpretation: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology., Funding: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)".

Background: Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes., Methods: We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes., Results: Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred., Conclusion: In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients.

Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress-related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy., Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence., Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (-0.08, 95% confidence interval -0.15 to -0.02, P=.016)., Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Although breast cancer remains a major cause of cancer death, its related death rate has dropped in the last years through early tumor detection and better available treatments. With the development of innovative techniques and new molecules as well as new routes of administration, local treatment and adjuvant therapy of early breast cancer have evolved, from mutilating, time-consuming and/or painful procedures to breast-conservative ones, sparing healthy tissues, reducing the total dose of treatment and the treatment time which in turn reduce the occurrence and severity of toxicity. In parallel with these improvements leading to an increase in survival rate, patients' health-related quality of life has become a major concern. This review aims at describing the evolution of early breast cancer treatment, and its impact on patients' quality of life, convenience, and satisfaction, including a special insight into emerging human epidermal growth factor receptor 2 (HER2)-targeted therapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Breast cancers are highly radiosensitive since the risk of recurrences and of mortality after adjuvant radiotherapy following breast-conserving surgery is decreased by 15.7% and 3.8%, respectively at 10 years. The total dose if irradiation also significantly increases local control: a boost of 16 Gy to the tumour bed after breast-conserving surgery reduces the absolute risk of recurrence by 4% at 10 years. Breast cancers are sensitive to the dose per fraction, as shown by the results from four randomized trials which compared standard irradiation (50 Gy/25 fractions) with a hypofractionated scheme: no statistical difference was observed in locoregional recurrence and overall survival at 10 years. The α/β ratio, which reflects the dose per fraction and is theoretically over 10 Gy for tumour tissues, has been estimated between 2.2 and 4.4 Gy for breast cancers. Molecular abnormalities, such as overexpression of HER1 (especially in triple negative breast cancer) and HER2, induce a higher radioresistance. In vitro studies showed that targeted therapies, which block these receptors, increase breast cancer radiosensitivity. Tumour stem cells have been identified in breast cancers and are characterized by a higher radioresistance. This radioresistance could be related to a better repair of radiation-induced DNA damages and a decrease of reactive oxygen species (ROS), which are involved in their occurrence. In the future, a better understanding of genetics tumour abnormalities will allow to identify new radiosensitivity settings in breast cancers., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Treatment volume is a major risk factor of radiation-induced toxicity. As nodal irradiation increases treatment volume, radiation toxicity should be greater. Nevertheless, scientific randomised data do not support this fact. However, a radiation-induced toxicity is possible outside tangential fields in the nodal volumes not related to breast-only treatment. Treatment should not be adapted only to the disease but personalized to the individual risk of toxicity for each patient., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

In addition to achieve breast conserving surgery after neoadjuvant chemotherapy, its indications are growing, especially in Her2 overexpressing and triple negative breast cancers owing to the emergence of new targeted therapies. Radiotherapy belongs to breast cancer management. However, some questions are still unresolved regarding nodes area irradiation after neoadjuvant chemotherapy. This short communication reviews indications of radiotherapy of node areas in breast cancer after neoadjuvant chemotherapy., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Irradiation of node areas is still a complex challenge in external radiotherapy for breast cancer. Acceptable target coverage is always balanced by protection of organs at risk and patient morphology. Intensity-modulated radiotherapy increases the quality of dose distribution on the planning target volume, but modifies dramatically the irradiation coverage of critical structures in a different way compared to 3D treatment. In this paper we analyze this new technique in breast treatment with node regions, its expected gain and potential risks., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer., Patients and Methods: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts., Results: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings., Conclusion: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The purpose of new radiotherapy techniques is to better deliver dose conformation in the tumour volume while diminishing organs at risk exposition. Their development is soaring in the breast cancer field in the adjuvant setting with intensity-modulated radiation therapy but also in cerebral and extracerebral oligometastastic presentation. Their usage is still being debated for breast cancer care. The objective of this narrative review is to list and discuss clinical data at our disposal for these news technologies., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Hormone receptors are expressed in more than 75% of breast cancer. Therefore, two prescription modalities of endocrine therapy could be proposed: either sequential or concomitant to breast cancer irradiation. If combined to radiotherapy, is endocrine therapy a radiosensitizer? Does endocrine therapy enhance the risk factor of radio-induced toxicity? Here, we will distinguish the interaction of ionizing radiation combined with therapies targeting oestrogen receptor (REα) from the interaction of ionizing radiation with oestrogen. This review aims at making clear all these items.

Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

One-day breast carcinoma treatment is defined as association of ambulatory surgery and intra-operative irradiation. Selection and rigorous process of patients is the key to success. The surgical technique is not changed by the radiotherapy. Patient's satisfaction index is very high. Financial loss should not be a hurdle to its implementation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The overexpression of the human epidermal growth factor receptor type 2 (HER-2) is an independent prognostic factor of poor outcome in patients with breast cancer. Two compounds have been registered for HER-2-positive tumour treatment: trastuzumab, a humanised antibody directed against the HER-2 extracellular domain, and lapatinib, a small molecule acting as a dual EGF-R and HER-2 tyrosine kinase inhibitor. Although both drugs improve progression-free survival, many patients' tumours will exhibit primary resistance, or develop secondary resistance, to anti-HER-2 therapies. The recent significant improvement of survival gained with pertuzumab (an antibody disrupting dimerisation of the receptor) or trastuzumab emtansine (T-DM1, a cytotoxic drug vectored by trastuzumab binding) opened the way for new registrations. This review describes the molecular mechanisms by which tumour cells may adapt to and evade HER-2 inhibition by HER-2-targeted therapies and discusses strategies to prevent and overcome resistance to trastuzumab and lapatinib. These strategies may include the establishment of predictive markers, exploration of combination therapies and modulation of nodal targets., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Owing to breast cancer screening, breast cancer is more and more diagnosed at early stage. For those breast cancer women, breast conserving treatment (breast conserving surgery followed by whole breast irradiation) is commonly used since many years. New radiation modalities have been recently developed in early breast cancers particularly accelerated partial breast irradiation (APBI). Among all techniques of radiotherapy, 3D-conformal APBI and intraoperative radiotherapy (IORT) are the main modalities of radiotherapy used. The present review states on indications, treatment modalities and updated results of local control and side effects of partial breast irradiation.

In the era of high-tech radiotherapy, hypofractionated schema is more and more widely used regardless of tumour sites. In this article, we expose the role, techniques and indications of hypofractionated radiotherapy in adjuvant breast radiotherapy., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Introduction: Brain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population., Patients and Methods: Breast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study., Results: 250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR-/HER2-), 30.8% as HR+/HER2- and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9-10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001)., Conclusions: Biological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The Montpellier cancer institute phase II trial started in 2004 and evaluated the feasibility of intraoperative radiotherapy (IORT) technique given as a sole radiation treatment for patients with an excellent prognostic and very low recurrence risk., Methods: Forty-two patients were included between 2004 and 2007. Inclusion criteria were patients ≥ 65 years old, T0-T1, N0, ductal invasive unifocal carcinoma, free-margin > 2 mm. IORT was delivered using dedicated linear accelerator. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electrons. In vivo dosimetry was performed for all patients. Primary end-point was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, specific and overall survival., Results: At inclusion, median age was 72 years (range, 66-80). Median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Late cosmetic results were good at 5 years despite the poor agreement of accuracy assessment between patients and physicians. Four patients (9.5%) experienced a local failure and underwent salvage mastectomy. The 5 year-disease free survival is 92.7% (range 79.1-97.6). All patients are still alive with a median follow-up of 72 months (range 66-74)., Conclusion: Our results confirm with a long-term follow-up that exclusive partial breast IORT is feasible for early-breast cancer in selected patients. IORT provides good late cosmetics results and should be considered as a safe and very comfortable "one-step" treatment procedure. Nevertheless, patient assessments are essential for long-term quality results.

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 © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Several prognostic indexes (PI) have been developed in the brain metastases (BM) setting to help physicians tailor treatment options and stratify patients enrolled in clinical studies. The aim of our study was to compare the clinical relevance of the major PI for breast cancer BM., Methods: Clinical and biological data of 250 breast cancer patients diagnosed with BM at two institutions between 1995 and 2010 were retrospectively reviewed. The prognostic value and accuracy of recursive partitioning analysis (RPA), graded prognostic assessment (GPA), basic score for BM (BS-BM), breast RPA, breast GPA, Le Scodan's Score and a clinico-biological score developed in a phase I study (P1PS) were assessed using Cox regression models. PI comparison was performed using Harrell's concordance index., Results: After a median follow-up of 4.5 years, median overall survival (OS) from BM diagnosis was 8.9 months (CI 95%, 6.9-10.3 months). All PI were significantly associated with OS. Harrell's concordance indexes C favored BS-BM and RPA. In multivariate analysis, the RPA, Le Scodan's score and GPA were found to be the best independent predictors of OS. In multivariate analysis restricted to the 159 patients with known LDH and proteinemia, RPA 2 and 3, Le Scodan's Score 3 and P1PS 2/3 were associated with worse survival. RPA was the most accurate score to identify patients with long (superior to 12 months) and short (inferior to 3 months) life expectancy., Conclusions: RPA seems to be the most useful score and performs better than new PI for breast cancer BM.

Intensity modulated radiotherapy (IMRT) is a technique allowing dose escalation and normal tissue sparing for various cancer types. For breast cancer, the main goals when using IMRT were to improve dose homogeneity within the breast and to enhance coverage of complex target volumes. Nonetheless, better heart and lung protections are achievable with IMRT as compared to standard irradiation for difficult cases. Three prospective randomized controlled trials of IMRT versus standard treatment showed that a better breast homogeneity can translate into better overall cosmetic results. Dosimetric and clinical studies seem to indicate a benefit of IMRT for lymph nodes irradiation, bilateral treatment, left breast and chest wall radiotherapy, or accelerated partial breast irradiation. The multiple technical IMRT solutions available tend to indicate a widespread use for breast irradiation. Nevertheless, indications for breast IMRT should be personalized and selected according to the expected benefit for each individual., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Prognosis of early breast cancer patients is significantly improved with the use of adjuvant therapies. Various guidelines have been proposed to select patients who will derive the most benefit from such treatments. However, classifications have limited usefulness in subsets of patients such as those with node negative breast cancer. The 2007 St. Paul de Vence Clinical Practice Recommendations proposed to consider adjuvant therapy in accordance with the 10-year relapse-free survival reduction estimated by Adjuvant! Online. However, many limitations remain regarding the use of Adjuvant! Online. Among them, adverse prognostic and/or predictive factors such as vascular invasion, mitotic activity, progesterone receptor negativity, and HER-2 expression are not incorporated in the routine clinical decision process. Our group has therefore issued guidelines based on the consideration of both Adjuvant! Online calculations and the prognostic and/or predictive effects of these markers. In addition, web-accessible comprehensive tables summarizing these recommendations are provided., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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 © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Various subgroups of breast tumours have been identified during the last 10 years according to the risk of local relapse. Prognostic factors for local relapse are age, surgical margins, tumour size, Her2 expression and hormonal receptors status. For tumours with a high risk of local relapse, an increased in boost dose or the addition of new drugs (trastuzumab, antiangiogenics, PARP inhibitors) could be considered. For low risk tumours, hypofractionated, accelerated partial breast and intraoperative radiotherapy are being evaluated. The classical schedule (45-50 Gy to the whole gland followed by a boost dose of 16 Gy) is no longer the universal rule. Treatment individualization, according to clinical and biological characteristics of the tumour and - possibly - to the radiobiological profile of the patient, is likely to be the future of breast cancer radiotherapy., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The use of intraoperative radiation therapy in breast cancer patients started about 20 years ago. Several retrospective and prospective studies have been published. Intraoperative radiation therapy was initially given as a boost to the tumour bed, followed by whole-breast irradiation. These studies have demonstrated the feasibility of the technique, with local control rates and cosmetic results similar to those obtained with standard treatments. Accelerated partial breast irradiation yields local recurrence rates as low as those observed after whole-breast irradiation. Intraoperative radiation therapy as a single irradiation modality with a unique dose has been investigated in recent prospective studies showing satisfactory local results. Intraoperative radiation therapy can be proposed either as a boost or as a unique treatment in selected cases (tumour size, nodal and hormonal status, patient's age). Intraoperative radiation therapy can be delivered by orthovoltage (50 kV) X-rays from mobile generators, or by electrons from linear accelerators, mobile or fixed, dedicated or not to intraoperative radiation therapy., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: While new strategies for the treatment of invasive breast cancer (BC) are emerging, radiotherapy (RT) modalities are still under debate. The French expert review board of Nice-Saint-Paul de Vence was asked firstly to conduct a qualitative evidence-based systematic review and then to establish clinical practice guidelines for the use of post operative RT in invasive BC., Methods and Materials: A search to identify eligible studies was undertaken using the Medline® database. All phase III randomized trials and systematic reviews evaluating the role and modalities of RT in invasive BC were included, together with some noncontrolled studies if no randomized trials were identified. The quality and clinical relevance of the studies were evaluated to determine the level of evidence., Results: The maximum delay between surgery and RT should ≤8 weeks when chemotherapy (CT) is not indicated. This should not exceed 24 weeks when adjuvant CT is administered. Whole breast RT delivering 50 Gy in 25 fractions followed by a boost of 10-16 Gy remains the standard of care after conservative surgery (CS). In the elderly population, for certain cases presenting comorbidities associated with a limited life expectancy, RT indication (even hypofractioned) and boost delivery may be unnecessary in the light of an unfavourable risk/benefit ratio. RT technique and indications should not vary in case of neoadjuvant CT followed by CS. After total mastectomy, RT should be indicated in N+ and in N- patients with high risk of local recurrence. The experts recommend to initiate tamoxifen at the end of RT, while aromatase inhibitors could be administered either concomitantly or sequentially with RT. There is no consistent data to delay (or suspend) trastuzumab administration during RT. As for all patients, in case of concurrent RT-trastuzumab administration, reduction of cardiac tissues exposure is highly recommended. After breast reconstruction, RT should be delivered as after standard CS without boost., Conclusion: Due to significant variations in practice in the treatment of patients with BC, our group aimed to provide guidelines for clinical practice. The systematic review of the literature formed the basis of our evidence-based recommendations; however expert agreements were necessary on those subjects that are still under debate. Our group will update these guidelines every 4 years, taking in consideration new advances in technology, new drugs administration, biologic tools and innovative therapeutic options., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)