EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Indirect pulp capping versus pulpotomy for treating deep carious lesions approaching the pulp in primary teeth: a systematic review.

AIM: To assess dental practice regarding the use of indirect pulp capping or pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and to compare the efficacy of the two pulp treatments. STUDY DESIGN: Systematic review. We searched the Cochrane Library, PubMed via MEDLINE, and EMBASE as well as the reference lists of included reports and ClinicalTrials.gov (for ongoing trials). Eligible studies were surveys of dental practice sent to dentists regarding the use of indirect pulp capping and pulpotomy in children with deep carious lesions approaching the pulp in primary teeth and any type of clinical study. Two review authors independently extracted data and assessed risk of bias in duplicate. RESULTS: Of the 481 potentially eligible articles, 11 were included in the review: 8 described surveys of dental practice, 1 a non-randomised study, and 2 ongoing randomised trials. The surveys of dental practice showed an overall increase in the teaching and practice of indirect pulp capping in primary teeth. The non- randomised study found a statistically significant difference in favour of indirect pulp capping for clinical and radiological success at 3 years but with high overall risk of bias. CONCLUSIONS: Despite the success rate of indirect pulp capping for treating deep carious lesions approaching the pulp in primary teeth, practitioners still hesitate to practice this technique because of lack of evidence and studies on this topic. Thus, for strong evidence, investigators are encouraged to conduct randomised trials comparing the efficacy of indirect pulp capping and pulpotomy for treating deep carious lesions approaching the pulp in primary teeth.

Cost of Chronic and Episodic Migraine. A pilot study from a tertiary headache centre in northern Italy.

BACKGROUND: Chronic migraine (CM) has a high impact on functional performance and quality of life (QoL). CM also has a relevant burden on the National Health Service (NHS), however precise figures are lacking. In this pilot study we compared the impact in terms of costs of CM and episodic migraine (EM) on the individual and on the National Health System (NHS). Furthermore, we comparatively evaluated the impact of CM and EM on functional capability and on QoL of sufferers. METHODS: We enrolled 92 consecutive patients attending the Pavia headache centre: 51 subjects with CM and 41 with episodic migraine (EM). Patients were tested with disability scales (MIDAS, HIT-6, SF-36) and with an ad hoc semi-structured questionnaire. RESULTS: The direct mean annual cost (in euro) per patient suffering from CM was €2250.0 ± 1796.1, against €523.6 ± 825.8 per patient with EM. The cost loaded on NHS was €2110.4 ± 1756.9 for CM, €468.3 ± 801.8 for EM. The total economic load and the different sub-items were significantly different between groups (CM vs. EM p = 0.001 for each value). CM subjects had higher scores than EM for MIDAS (98.4 ± 72,3 vs 15.5 ± 17.7, p = 0.001) and for HIT-6 (66.1 ± 8.4 vs 58.7 ± 10.1, p = 0.001). The SF-36 score was 39.9 ± 14,74 for CM and 66.2 ± 18.2 for EM (p = 0.001). CONCLUSIONS: CM is a disabling condition with a huge impact on the QoL of sufferers and a significant economic impact on the NHS. The adequate management of CM, reverting it back to EM, will provide a dual benefit: on the individual and on the society.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Allergy to beer in LTP-sensitized patients: beers are not all the same.

BACKGROUND: Most cases of beer allergy reported so far have been associated with hypersensitivity to the non-specific lipid transfer protein (LTP). In view of the marked differences in brewing processes we assessed IgE reactivity as well as tolerance to many different beers in an allergic patient. METHODS: A 45 year-old man hypersensitive to grass pollen, cat dander and Alternaria tenuis with a history of urticaria and dyspnoea after drinking beer and a weak skin reactivity to commercial corn extract was studied. The patient underwent SPT with 36 different brands of beer and an open challenge with those scoring negative was performed. An immunoblot analysis was carried out using 2 SPT-positive beers, 2 SPT-negative beers, and barley, wheat, and maize extracts using both patient's serum and a maize LTP-specific in-house developed polyclonal antibody from rabbit. Further, the immune reactive LTP of one beer was separated by HPLC and the chromatogram was compared to that of purified maize LTP. RESULTS: Beer SPT scored positive in 30/36 cases. The immunoblot analysis showed IgE reactivity at about 10 kDa against the two SPT-positive beers and against maize with both patient's serum and the polyclonal anti-LTP rabbit serum, whereas the two SPT-negative beers, and barley extract scored negative. The immunodetected protein co-migrated with maize LTP. CONCLUSION: In beer-allergic patients the diagnostic workup may point to the detection of some tolerated products that can be consumed risk-free.

Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment.

Intermittent preventive treatment in pregnancy (IPTp) is used to prevent Plasmodium falciparum malaria. However, parasites resistant to the IPTp drug sulfadoxine-pyrimethamine (SP) have emerged worldwide, and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice. In a prospective delivery cohort in Muheza, Tanzania, we examined the effects of SP IPTp on parasite resistance alleles, parasite diversity, level of parasitemia, and inflammation in the placenta. IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581, an increase in the level of parasitemia, and more intense placental inflammation. The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use. These findings support a model of parasite release and facilitation, whereby the most highly resistant parasites out-compete less fit parasite populations and overgrow under drug pressure. Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance.

DMF from WHO basic methods to ICDAS II advanced methods: a systematic review of literature.

BACKGROUND: Evaluation of caries status has changed with emergence of modified ways of managing the condition. There is a need to assess the relationship between the old and new methods of registering caries. OBJECTIVE: To identify the ICDAS II codes to be used to record the D-component of the DMF index as defined in the WHO Basic Methods, 1997 publication. METHOD: A review of literature published between January 2002 and January 2012 was undertaken using "ICDAS" as keyword in an electronic search. Only epidemiological studies that used ICDAS II as an evaluation criterion calculated the DMF indices and gave the ICDAS II codes for the diagnosis of caries lesions, were included. RESULTS: Fourteen studies met the inclusion criteria. The DMF designations that corresponded with the WHO definition were D(3-6)MF (10 studies), D(4-6)MF (4 studies) or D(5-6)MF (3 studies). The D-component referred to cavitated carious lesions (7 studies) or dentine caries (7 studies), but there was no consensus on the ICDAS II codes that are used to define them. Only the ICDAS II codes 5 and 6 had unanimous support; they were always counted as "Caries", but there was less certainty for codes 3 and 4. The only study on fields that compared both methods showed D(3-6) to be the always associated with the D-component of the DMF index as defined in the WHO Basic Methods. CONCLUSION: There was disagreement of the ICDAS II codes to be used for the DMF calculation; and when there was a need to compare DMF values between studies, the diagnosis threshold should be verified to be the same.

Habituation of evoked responses is greater in patients with familial hemiplegic migraine than in controls: a contrast with the common forms of migraine.

BACKGROUND: Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of migraine with transient hemiplegia during the aura phase. Mutations in at least three different genes can produce the FHM phenotype. The mutated FHM genes code for ion transport proteins that animal and cellular studies have associated with disturbed ion homeostasis, altered cellular excitability, neurotransmitter release, and decreased threshold for cortical spreading depression. The common forms of migraine are characterized interictally by a habituation deficit of cortical and subcortical evoked responses that has been attributed to neuronal dysexcitability. FHM and the common forms of migraine are thought to belong to a spectrum of migraine phenotypes with similar pathophysiology, and we therefore examined whether an abnormal habituation pattern would also be found in FHM patients. METHODS: In a group of genotyped FHM patients (five FHM-1, four FHM-2), we measured habituation of visual evoked potentials (VEP), auditory evoked potentials including intensity dependence (IDAP), the nociception-specific blink reflex (nsBR) and compared the results to a group of healthy volunteers (HV). RESULTS: FHM patients had a more pronounced habituation during VEP (P=0.025) and nsBR recordings (P=0.023) than HV. There was no difference for IDAP, but the slope tended to be steeper in FHM. CONCLUSION: Contrary to the common forms of migraine, FHM patients are not characterized by a deficient, but rather by an increased habituation in cortical/brain stem evoked activities. These results suggest differences between FHM and the common forms of migraine, as far as central neuronal processing is concerned.

Clinical decision on pit and fissure sealing according to the occlusal morphology. A descriptive study.

BACKGROUND: The objective of this descriptive study was to evaluate the clinical decision on sealing pits and fissures according to the occlusal morphology in patients with low individual caries risk (ICR). MATERIALS AND METHODS: A total of 222 dentists, 86 affiliated to the French Society of Paediatric Odontology (SFOP) and 136 general practice dentists (GPs), answered the same questionnaire with illustrations of 4 occlusal surfaces of permanent molars: they indicated firstly if these were at risk and secondly the corresponding decision regarding sealing. This questionnaire assessed the decision on widening pits and fissures before sealing and the type of sealant material used. Multivariate logistic regression analyses were performed to identify the factors associated with the clinical decision to widen pits and fissures. RESULTS: Sealing of at-risk teeth was indicated by 89% of dentists, whereas sealing of not at-risk occlusal surfaces was recommended by 46%. SFOP dentists were more prone to recommend pit and fissures sealants. The multivariate analyses demonstrated that only the type of material was associated with the clinical decision to widen pits and fissures. Forty eight percent of dentists choose the same material in all clinical situations. CONCLUSION: The wide variations in sealant use and placement technique implies there is no apparent consensus among GP and SFOP dentists. Although the criteria are similar in numerous scientific societies, not all dentists are acting upon these recommendations.

Deep carious lesions management in children and adolescents: a questionnaire survey among dentists practicing paediatric dentistry in France.

INTRODUCTION: While many questionnaire surveys have been undertaken worldwide to investigate practices toward deep carious lesion (DCL) management in adults, very few are related to children and adolescents. The present cross-sectional study aimed to assess DCL management in children and adolescents among dentists practicing paediatric dentistry in France (Fr-DPPDs). The secondary objective was to compare practices between Fr-DPPDs and dentists registered in the European Academy of Paediatric Dentistry (EAPD). METHODS: A questionnaire was electronically administrated to members of the CEOP (Collège des Enseignants en Odontologie Pédiatrique), the SFOP (Société Française d'Odontologie Pédiatrique), and the EAPD. Descriptive analyses, Chi-square and McNemar tests, ANOVA, crude and adjusted binary logistic regression analyses were performed. RESULTS: A total of 99 Fr-DPPDs and 146 EAPD members answered the questionnaire. Among the Fr-DPPDs, the preferred caries removal (CR) methods were the complete CR in one step for primary teeth and mature permanent teeth (respectively, 70% and 48%) and in two steps for immature permanent teeth (39%). EAPD members were more likely, than Fr-DPPDs, to choose selective CR versus complete CR in primary teeth (odds ratio = 2.60; 95% CI 1.39-4.85). Moreover, for primary or immature permanent teeth, general practitioners were less likely to choose selective CR than specialists and exclusive practitioners in paediatric dentistry, (p < 0.001). CONCLUSION: Tooth type [primary, permanent (immature or mature)] seemed to influence DCL management. Fr-DPPS should prioritise pulpal vitality when managing DCL.

Restorative thresholds for carious lesions in primary molars: French dentist's decisions.

PURPOSE: Questionnaire surveys have been undertaken worldwide to investigate practices and knowledge related to carious lesion management, particularly in adults. The primary objective of this cross-sectional survey was to investigate restorative thresholds (RTs) used for carious lesions in primary molars by dentists practising paediatric dentistry in France. Dentists were surveyed by a specifically developed questionnaire based on clinical and radiographic caries classifications. The secondary objective was to explore restorative management strategies in primary molars. METHODS: A structured questionnaire assessing RTs and management strategies for occlusal and approximal carious lesions of primary molars was anonymously and electronically administered via SurveyMonkey® to dentists who were members of the Société Française d'Odontologie Pédiatrique. Descriptive analyses, Chi-square test, McNemar test, and logistic regression analyses considering dependent RT variables for occlusal and approximal carious lesions were performed. RESULTS: Among 250 dentists surveyed, 201 responded (response rate 80.4%). Overall, 43% (n = 87) and 75% (n = 151) of respondents would place their RTs in enamel for occlusal and approximal lesions, respectively. Dentists with an exclusive practice of paediatric dentistry more frequently would choose a RT in dentine for approximal lesions than did other dentists (p = 0.010). A preparation technique including sound dental tissues was less frequent for occlusal than approximal lesions (n = 31; 15% vs n = 60; 30%). Overall, 75% (n = 151) of respondents used the same restorative material for occlusal and approximal lesions. CONCLUSION: In general, dentists practising paediatric dentistry in France overtreated lesions on primary molars, which contradicts minimal intervention recommendations. RTs are too often indicated for enamel-confined carious lesions.

[Combined hormonotherapy with external beam radiotherapy in locally advanced prostate cancer: do side effects overlap the advantages?]. / Hormonothérapie combinée à la radiothérapie externe dans le cancer de prostate localement avancé: les effets secondaires contrecarrent-ils les bénéfices?

Used for more than 60 years in metastatic prostate cancers, hormone therapy is nowadays also an option for the treatment of locally advanced prostate cancer. Adjuvant androgen deprivation combined with external beam radiotherapy has become the gold standard treatment in locally advanced prostate cancer. Combined therapy has been extensively investigated and has shown to improve oncologic outcomes. However, its toxicity is not negligible. Several side effects can be encountered: cardiovascular, bone depletion, metabolic changes and neuropsychologic effects. They may overlap treatment benefits and be responsible of a specific mortality. Nevertheless, randomized studies have demonstrated that there was no increase of specific mortality from combined treatments compared to patients treated by radiotherapy alone. Therefore, these side effects might not be a barrier to adjuvant androgenic deprivation. However, long-term results are still needed and also accurate morbidity studies. In addition, the debate is still ongoing regarding the appropriate duration of hormone therapy.

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group.

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.

Implementation and evaluation of existing guidelines on the use of neurophysiological tests in non-acute migraine patients: a questionnaire survey of neurologists and primary care physicians.

BACKGROUND AND PURPOSE: The main aims of this study were to evaluate: the diffusion, use and perception of the usefulness of the 2004 EFNS guidelines on neurophysiological testing in non-acute headache patients; the frequency with which the different neurophysiological tests were recommended in non-acute migraine patients by physicians aware or unaware of the guidelines; and the appropriateness of the reasons given for recommending neurophysiological tests. METHODS: One hundred and fifty physicians selected amongst the members of the Italian societies of general practitioner (GPs), neurologists and headache specialists were contacted via e-mail and invited to fill in a questionnaire specially created for the study. RESULTS: Ninety-two percent of the headache specialists, 8.6% of the neurologists and 0% of the GPs were already aware of the EFNS guidelines. A significantly higher proportion of headache specialists had not recommended any neurophysiological tests to the migraine patients they had seen in the previous 3 months, whereas these tests had frequently been prescribed by the GPs and neurologists. Overall, 80%, 42% and 42.6% of the reasons given by headache specialists, neurologists and GPs, respectively, for recommending neurophysiological testing in their migraine patients were appropriate (P < 0.01). CONCLUSIONS: The diffusion of the EFNS guidelines on neurophysiological tests and neuroimaging procedures was found to be very limited amongst neurologists and GPs. The physicians aware of the EFNS guidelines recommended neurophysiological tests to migraine patients less frequently and more appropriately than physicians who were not aware of them. The most frequent misconceptions regarding neurophysiological tests concerned their perceived capacity to discriminate between migraine and secondary headaches or between migraine and other primary headaches.

[Report of the mission commissioned by the Ministry of Health to the French Society of Radiation Oncology]. / Rapport de la mission confiée par le ministère de la Santé à la Société française de radiothérapie oncologique.

Further to the Epinal events, Health Ministers P. Bas then R. Bachelot-Narquin have launched a plan of work devoted to radiotherapy; they have also committed the SFRO President, within the framework of a mission, to make proposals taking into account the demography of professionals and their level of competence, valorization of careers, cooperation with medical oncologists, delegations of authorities, mutualisation of human and material resources. Due to the numerous actions of the roadmap managed by the tutelages, the aim of the mission was focused on the modalities of work of the professionals linked to radiotherapy: radiation oncologists, radiographers and physicists.

Carious lesion management in children and adolescents by Australian dentists.

BACKGROUND: The management of carious lesions in children and adolescents can have lifelong implications for the patient. The aim of this study was to assess the decision-making process of dentists when managing carious lesions in children and adolescents. METHODS: Approximately, 11 000 dentists listed as members of the Australian Dental Association Inc. (ADA) and Australian and New Zealand Society of Paediatric Dentistry (ANZSPD) were emailed a link in April 2017 to a 19-question survey delivered by SurveyMonkey™. RESULTS: In this study, 887 responses were received. In 'enamel-limited' carious lesions, dentists intervened most frequently in primary tooth approximal (365, 41.1%), followed by permanent tooth occlusal (295, 33.3%) and approximal (244, 27.5%), and primary tooth occlusal (203, 22.9%) surface carious lesions. Age, university of graduation, practicing state, decade of graduation and frequency of treatment of children between 6 and 15 years were significant demographic factors influencing the restorative threshold. CONCLUSIONS: Australian dentists reported significant variation in their management of approximal and occlusal carious lesions in both primary and permanent teeth. A substantial proportion of respondents would intervene surgically on non-cavitated enamel-limited lesions.

[Increasing quality and safety of external radiation treatments: actions of the French Society of Radiation Oncology (SFRO)]. / Qualité en radiothérapie: les actions de la société française de radiothérapie oncologique (SFRO).

Accidents which recently occured in external radiotherapy led the French Ministry of Health to implement a programme aimed at increasing quality and safety of treatments. We report the actions of the French society of radiation oncology in the field of this programme called Feuille de route.

The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 "boost versus no boost" trial.

PURPOSE: To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer. PATIENTS AND METHODS: Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented. RESULTS: At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively. CONCLUSION: An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.