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Abstract Background Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. Methods/Design The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE100C*6 versus FE100C*3 followed by Docetaxel100*3). Discussion In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE100C-Docetaxel100, and 1,327 received French FE100C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. Trial Registration clinical Trials.gov NCT01222052.

Bisphosphonates, such as pamidronate, are a new class of drugs, initially described for treatment of neoplasic hypercalcemia. Currently, they also may be used in the treatment of bone metastases from solid tumor, even without hypercalcemia. Hypocalcemia is a potential adverse effect of these drugs, which is considered infrequent and rarely symptomatic. We describe three cases of severe hypocalcemia following one injection of pamidronate. The three patients had bone metastases from solid tumors (breast in two cases, prostate in one), at least partially osteoblastic, and none had hypercalcemia. The induced hypocalcemia was rapid in onset, severe, and durable. The mechanism seems to be multiple and may include both the expected reduction of osteolysis and also a rapid and direct action on parathyroid glands followed by resistance to parathormone. Some elements could amplify the phenomenon, such as latent hypoparathyroidism after surgery, cervical radiotherapy, hypomagnesemia, or low 25 hydroxy vitamin D (25OH D). For patients who have such risk factors, it may be useful to check calcium several days after the first injection. [ABSTRACT FROM AUTHOR]

Background: Risk assessment in node-negative (N0) breast cancer patients (pts) is routinely performed by established clinico-pathological algorithms (CP) (Schmidt et al. Ann Oncol 2009). ASCO guidelines also recommend invasion markers uPA/PAI-1 (UP; Harris et al. JCO 2007). The prospective randomized multicenter NNBC 3-Europe trial had two questions: 1) Does UP compared to the CP algorithm improve identification of low-risk node-negative breast cancer patients? 2) Does addition of taxanes to adjuvant chemotherapy improve DFS probability in high-risk node-negative breast cancer? Data are mature to report on the second question only. Methods: Between 2002 and 2009, 4,147 node-negative breast cancer pts were recruited. Risk assessment was performed by CP (43 %) or by UP (57 %). High-risk pts were randomized to receive FE100C*3-Doc*3 (FEC-D) versus FE100C*6 (FEC) as adjuvant chemotherapy. Primary endpoint was disease-free survival probability (DFS). It was planned to accrue 2,572 pts allowing detection of 4% reduction in recurrence probability at 5 years with a power of 80 % at a level of α=0.05 (LogRank) after a minimum observation time of 2.5 years for every recruited patient. Results: In the intent-to-treat population (ITT, n=2,541), 1,286 high-risk pts received FEC-D, and 1,255 received FEC. In July 2012, 90.8 % of patients had reached the minimum observation time - median follow-up was 43.8, and 44.4 months. Main patients' characteristics were distributed similarly between the two chemotherapy arms: median age was 53 yrs, 37.4 % of pts were premenopausal, median tumor size was 1.90 cm, grade 3 was seen in 53.8 %, hormone receptor status was negative in 30.1 % and HER2 was overexpressed in 20.0 %. Mastectomy was performed in 11 %. All planned courses of FEC-D were given in 84.4 %, of FEC in 91.4 % (p < 0.0001). DFS after 2.5 yrs was for FEC-D 97.5 % (+/- 0.45 %) and for FEC 97.3 % (+/- 0.47 %). Overall-survival probability (OS) after 2.5 yrs was 99.0 % (+/- 0.29 %) for FEC-D and 99.5 % (+/- 0.20 %) for FEC. The survival differences between the two arms were not statistically significant. Per-protocol analysis did not reveal any additional results. Conclusions: Use of taxanes does not further reduce the rate of early recurrences and led to significantly more treatment discontinuation. Today, with adequate adjuvant chemotherapy even high-risk node-negative breast cancer patients have an excellent prognosis. [ABSTRACT FROM AUTHOR]

Background: Both peripherally inserted central catheters (PICCs) and implanted port catheters (PORTs) are used for adjuvant chemotherapy (ACT) administration in patients with early breast cancer (EBC). We aimed to compare the safety between PICCs and PORTs in this setting., Patients and Methods: This monocentric phase II randomised trial (NCT02095743) included patients with EBC who were eligible for ACT. Patients with curative anticoagulation therapy were excluded. The primary objective was to identify which device has a lower probability of catheter-related significant adverse events (CR-SAEs) within the 35 weeks after device implantation. The secondary objective was to evaluate quality of life (QoL) and patient satisfaction., Results: From February 2014 to May 2018, 256 patients were included, and 253 (99%) were analysed. Overall, 31 patients (12.2%) experienced CR-SAEs, which mainly included thromboembolic events. In an intention-to-treat analysis, the probability that a CR-SAE would occur was 7.8% (10 events) with PORTs versus 16.6% (21 events) with PICCs (hazard ratio [HR] = 2.2 [1.03-4.62], P = 0.036). In a per-protocol analysis, PICCs were also associated with a higher risk of CR-SAEs than PORTs (HR = 2.82 [1.26-6.25], P = 0.007). Regarding the secondary objectives, if there was no difference in QoL between the arms, then significantly more discomfort was reported among patients with PICCs than among patients with PORTs (P = 0.002 after implantation and P < 0.001 at mid-treatment or at the end of treatment)., Conclusions: CR-SAEs in patients with EBC are frequent but rarely impact the ACT process. Compared with PORTs, PICCs are associated with a significantly higher risk of CR-SAEs and more discomfort. PORTs should be preferred for ACT administration in patients with EBC., Competing Interests: Conflict of interest statement The authors have no conflict of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The likelihood of menses recovery varies greatly in premenopausal patients receiving adjuvant chemotherapy for breast cancer. Quantifying this probability for each patient could better inform the chemotherapy discussion and individualize fertility counseling. We performed a pooled analysis of the PACS04 and PACS05 adjuvant randomized trials to develop a nomogram to estimate the probability of menses recovery at 3, 6, and 18 months after the end of adjuvant chemotherapy., Patients and Methods: Women who were premenopausal and aged ≤ 50 years at randomization in the PACS04 and PACS05 trials were included in the present analysis. The primary endpoint was the probability of menses recovery within 18 months of chemotherapy completion. Multivariable Cox proportional hazards regression was used to estimate the association of each variable with the likelihood of menses resumption. A nomogram was developed to predict menses recovery at different intervals., Results: The factors associated with menses recovery were assessed for 1210 patients. At a median follow-up of 90 months (range, 3-189 months), 342 of 1210 patients (28.2%) had recovered menses. The probability of menses recovery at 18 months was 25.5% (range, 23.0%-27.9%). After backward elimination, age, final body mass index, type of chemotherapy, and hormone therapy were selected to build the nomogram to predict the probability of menstrual resumption at 3, 6, and 18 months after chemotherapy., Conclusion: An accurate and individualized prediction of menses recovery is feasible for premenopausal patients eligible for adjuvant chemotherapy for early-stage breast cancer. Our nomogram will be externally validated in a large prospective cohort., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years., Patients and Methods: BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported., Results: Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up., Conclusion: Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.

Background: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls., Patients and Methods: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status., Results: The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline., Conclusion: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC., Implications for Practice: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Background: Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors., Methods: Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT., Findings: Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p < 0.0001). Cardiovascular signs were strongly associated with allergy. Non-allergic IH was observed in 152 patients (62%) (ICM:134; GBCM:18). Severity grade was lower (p < 0.0001) and reaction delay longer (11.6 vs 5.6 min; p < 0.001). Potentially allergic IH was diagnosed in 42 patients (17.1%) (ICM:34; GBCM:8). The delay, severity grade, and mediator release were intermediate between the two other groups., Interpretation: Allergic IH accounted for < 10% of cutaneous reactions, and > 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.

Purpose: To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment., Patients and Methods: ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas., Results: Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome., Conclusion: ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

Background: The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC)., Patients and Methods: The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls ( n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index., Results: Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment ( p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel ( p = .05)., Conclusion: This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel., Implications for Practice: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (©AlphaMed Press.)

Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a marker of resistance to aromatase inhibitors in hormone receptor positive metastatic breast cancer. We retrospectively considered seven patients treated for metastatic breast cancer with available samples from the primary tumor before any treatment, cryopreserved metastasis removed during progression and concomitant plasmas. All these seven patients were in disease progression after previous exposure to aromatase inhibitors for at least 6 months, and were assessed for ESR1 mutations detection in tumor and circulating DNA. For these patients, Sanger sequencing identified four metastases with clear ESR1 mutation and one possible, whereas digital PCR identified six mutated metastases. Then, under blind conditions and using digital PCR, corresponding circulating ESR1 mutations were successfully detected in four of these six metastatic breast cancer patients. Moreover, in two patients with serial blood samples following treatments exposure, the monitoring of circulating ESR1 mutations clearly predicted disease evolution. In the context of high interest for ESR1 mutations, our results highlight that these acquired recurrent mutations may be tracked in circulating tumor DNA and may be of clinical relevance for metastatic breast cancer patient monitoring., (© 2015 UICC.)

Objectives: Preoperative biopsy of breast cancer allows for prognostic/predictive marker assessment. However, large tumors, which are the main candidates for preoperative chemotherapy, are potentially more heterogeneous than smaller ones, which questions the reliability of histologic analyses of needle core biopsy (NCB) specimens compared with whole surgical specimens (WSS). We studied the histologic concordance between NCB specimens and WSS in tumors larger than 2 cm., Methods: Early pT2 or higher breast cancers diagnosed between 2008 and 2011 in our center, with no preoperative treatments, were retrospectively screened. We assessed the main prognostic and predictive validated parameters. Comparisons were performed using the κ test., Results: In total, 163 matched NCB specimens and WSS were analyzed. The correlation was excellent for ER and HER2 (κ = 0.94 and 0.91, respectively), moderate for PR (κ = 0.79) and histologic type (κ = 0.74), weak for Ki-67 (κ = 0.55), and minimal for SBR grade (κ = 0.29). Three of the 21 HER2-positive cases (14% of HER2-positive patients or 1.8% of all patients), by WSS analysis, were initially negative on NCB specimens even after chromogenic in situ hybridization., Conclusions: NCB for large breast tumors allowed reliable determination of ER/PR expression. However, the SBR grade may be deeply underestimated, and false-negative evaluation of the HER2 status would have led to a detrimental lack of trastuzumab administration., (Copyright© by the American Society for Clinical Pathology.)

The RAPP-01 clinical trial compared two adjuvant chemotherapies, doxorubicin plus docetaxel (arm A) versus doxorubicin plus cyclophosphamide (arm B), in 627 women with breast cancer. It stopped prematurely when three severe adverse events occurred among patients with febrile neutropenia (FN), all in the arm A. FN occurred in 40.8% (126/311) in arm A versus 7.1% (22/316) in arm B. We investigated Single Nucleotide Polymorphisms (SNPs) in drug transporter and metabolism genes potentially incriminated in this excess of FN. Using a dedicated DNA chip, we tested association of SNPs belonging to 97 transporter and 68 metabolizing genes with FN occurrence in 155 patients enrolled in the RAPP-01 trial, 85 in arm A and 70 in arm B. Association study in the 85 patients receiving docetaxel identified two SNPs, rs4762699 and rs2857468, both located in the SLCO1A2 gene. Haplotype T-T was associated with a high risk of FN: 83.3% of patients with at least one copy of T-T versus 32.8% in patients with other haplotypes (odds ratio = 10.25, P = 1.4e-4). In a multivariate logistic model adjusted for treatment arm, effect of haplotype T-T remained significant (odds ratio = 6.84, P = 1.15e-4). FN in patients receiving docetaxel in the RAPP-01 trial is significantly associated with the haplotype T-T in rs4762699 and rs2857468 in the SLCO1A2 transporter gene. This result should be validated in an independent cohort.

Background: Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy., Methods: In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379., Findings: Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 6·3 months [95% CI 5·4-7·2] vs 4·2 months [3·9-4·7], respectively, stratified hazard ratio [HR] 0·75 [95% CI 0·61-0·93], two-sided stratified log-rank p=0·0068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone., Interpretation: These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy., Funding: F Hoffmann-La Roche., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients., Methods: Women >65years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD)., Results: Among the 123 elderly EBC patients (70±4years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P<.0001). Verbal episodic memory was mainly impaired (21% of patients). No correlation was observed between objective CD and cancer stage or geriatric assessment. Subjective CD only correlated with verbal episodic memory (P=.01)., Conclusions: This is the first large series assessing baseline cognitive functions in elderly EBC patients. More than 40% presented objective CD before any adjuvant therapy, which is higher than what is reported among younger patients. Our results reinforce the hypothesis that age is a risk factor for CD in EBC patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.

Background: Few data are published on docetaxel toxicity in obese patients., Patients and Methods: All obese patients (n=100) treated for early breast cancer during three consecutive years at our Institution, were retrospectively investigated. The same number of non-obese patients was randomly selected and used as controls. We assessed the factors predictive of the relative dose intesity (RDI) reduction, including body composition., Results: A total of 18% (n=18) of obese patients and 5% (n=5) of non-obese patients required reduction of docetaxel RDI due to toxicity (p=0.008). In a multivariate analysis, body mass index (BMI) and age were predictive of a reduction in RDI. Among the 89 patients with a determination of body composition, patients with a higher fat mass more frequently had a reduction in docetaxel RDI (p=0.002). In multivariate analysis, fat mass was the only independent factor predictive of a reduction in docetaxel RDI., Conclusion: Obese patients treated for early breast cancer more frequently required a reduction in docetaxel RDI. Fat mass seems to be the best factor predictive of a reduction in docetaxel RDI.

The efficacy of the combination bevacizumab-chemotherapy in the first-line treatment of metastatic breast cancer (mBC) was demonstrated in several randomized clinical trials. However, limited safety data is available in daily medical practice. ATHENA is an international phase-IIIb study conducted in 2,251 patients with locally advanced or mBC, treated in first-line with bevacizumab combined with taxanes-based chemotherapy. The primary objective is safety assessment. In France, 365 patients were included. Their median age was 56 years (24-93 years) and ECOG performance status was 0 or 1 in 93.9% of patients. Bevacizumab was essentially combined with a taxanes monotherapy: docetaxel (37.3%) or paclitaxel (28.8%) or taxanes-based combination therapy (9.4%). The most frequent grade superior or equal to 3 adverse event (AE) was neutropenia (34.5%). Grade superior or equal to 3 AEs of special interest related to bevacizumab were arterial and venous thromboembolism (5.1%), high blood pressure (4.2%), proteinuria (2.3%) and hemorrhage (2%). Median time to progression was 9.5 months (95% CI: 8.8-10.4). The safety profile and the efficacy of the combination bevacizumab-taxanes in a population more representative of daily oncology practice in France are comparable to those reported in clinical trials in mBC.

Purpose: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years., Patients and Methods: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days. Radiotherapy was mandatory after conservative surgery and tamoxifen was given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was the trial's main endpoint. Updated 8-year survival data are presented., Results: With a median follow-up of 92.8 months, 639 patients experienced at least one event. A total number of 383 deaths were registered. Eight-year DFS rates were 65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse and a 25% reduction in the relative risk of death in favor of FEC-D. Significant relative risk reductions were observed in the HR-positive, HER2-positive, and Ki67 ≥20% subpopulations., Conclusion: Benefits for DFS and OS rates with the sequential FEC-D regimen are fully confirmed at 8 years.

High-resolution computed tomography scanning (CT) allows depiction of microanatomic structures of the temporal bone. CT is useful for detecting several pathologic conditions of the temporal bone such as congenital malformations, particularly in young children with sensorineural hearing loss. Some external, middle and inner ear structures are difficult to evaluate. The objective of this study has been to provide the key planes in coronal and axial planes (five coronal planes and three axial planes) but also with oblique planes reconstruction (two planes) for normal temporal bones evaluation. These standardized planes help to improve visualization of the main congenital malformations. Identification of obvious morphogenetic malformations (Michel aplasia, Mondini deformity….) is not difficult. However, less severe dysplasia may be missed or normal micro anatomic structures in newborn misreaded., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

What Is Already Known About This Subject: • Functional polymorphisms on the VEGF-A gene, known to be linked to cancer risk or to VEGF-A plasma concentrations, have been identified. So far, limited knowledge has been published on the relationships between toxicity/efficacy of bevacizumab-based therapy and VEGF-A polymorphisms (tumoral DNA). We therefore prospectively tested the impact of these five gene polymorphisms (blood DNA) on the pharmacodynamics of bevacizumab-based treatment administered in metastatic breast cancer patients., What This Study Adds: • Present data obtained from a prospective study suggest a role for VEGF-A 936C > T polymorphism as a potential predictor of time to progression in breast cancer patients receiving bevacizumab-containing therapy. Also, the VEGF-A-634G > C polymorphism was linked to bevacizumab-related toxicity. AIMS To test prospectively the impact of VEGF-A gene polymorphisms on the pharmacodynamics of bevacizumab-chemotherapy in breast cancer patients., Methods: As part of the single-arm MO19391 trial, 137 women with locally recurrent or metastatic breast cancer receiving first-line bevacizumab-containing therapy were analysed. Patients received bevacizumab associated (76%) or not (24%) with taxane-based chemotherapy. Clinical evaluation included clinical response, time to progression (TTP) and a toxicity score corresponding to the sum of each maximum observed toxicity grade (hypertension, haemorrhage, arterial and venous thrombo-embolism). Functional VEGF-A polymorphisms at position -2578 C > A, -1498 T > C, -1154 G > A, -634 G > C and 936 C > T were analysed by PCR-RFLP (blood DNA)., Results: Overall response rate (complete response (CR) + partial response (PR)) was 61%. Median TTP was 11 months. None of the VEGF-A polymorphisms was significantly linked to clinical response. Analysis of the 936C > T polymorphism revealed that the 96 patients homozygous for the 936C allele exhibited a marked tendency for a shorter TTP (median 9.7 months) than the 32 patients bearing the 936T allele (median 11.5 months, P= 0.022) of which 30 were CT and two were homozygous TT. Other polymorphisms did not influence TTP. VEGF-A-634 G > C was significantly related to the toxicity score with 39%, 49% and 81% of patients with score >1 in GG, GC and CC patients, respectively (P= 0.01)., Conclusions: The role for VEGF-A 936C > T polymorphism as a potential marker of TTP in breast cancer patients receiving bevacizumab-containing therapy concords with the known impact of VEGF-A 936C > T polymorphism on VEGF-A expression., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Background: Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question., Methods/design: The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE(100)C*6 versus FE(100)C*3 followed by Docetaxel(100)*3)., Discussion: In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE(100)C-Docetaxel(100), and 1,327 received French FE(100)C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up., Trial Registration: clinical Trials.gov NCT01222052., (© 2011 Kantelhardt et al; licensee BioMed Central Ltd.)

Purpose: To determine the clinical feasibility of MR spectroscopy (MRS) of prostate cancer using external multi-channel surface coils at 1.5T. Materials and methods. Retrospective study of 31 patients with prostate cancer who underwent MRS as part of the staging work-up prior to radical prostatectomy. The ratio of the three main metabolites ([choline + creatine]/citrate) were measured along with spectral analysis of different regions of interest (ROI) placed in areas of normal tissue and cancer using the surgical specimen as the standard of reference., Results: One hundred and eighty-three voxels were analyzed. Qualitative visual analysis identified pathological spectra in 88.5% of cancer ROI, 11.7% of normal transitional zone ROI and 1.6% of normal peripheral zone ROI. The ratios of normal prostate tissue were significantly more elevated (p<0.0001) in the transition zone (0.41 +/- 0.24) than in the peripheral zone (0.22 +/- 0.36). Tumor containing voxels had significantly higher ratios (2.84 +/- 2.74) than normal tissue containing voxels of the transition zone (p<0.0001) and peripheral zone (p<0.0001)., Conclusion: Prostate MRS using external surface coils appears routinely feasible at 1.5T, even though it presents some limitations.

Purpose: Review the CT and MR imaging findings in patients with sudden deafness (SD)., Patients and Methods: Thirty-seven patients with SD were prospectively included. All patients underwent MR evaluation of the brain and temporal bones to exclude classical etiologies such as vestibular schwannoma. CT of the temporal bones was also performed to exclude lesions of the bony labyrinth. A total of 100 CT examinations of the temporal bone in control subjects were reviewed and measurements obtained to establish a reference standard to compare to findings in our patient population., Results: Findings included: vestibular schwannoma in 2.7%, labyrinthine hemorrhage in 8.1%, bony labyrinthine anomaly in 59.5% according to our criteria, and significantly more frequent than in our control subjects, including dehiscence of the superior semicircular canal in 8.1%, lateral semicircunal canal anomaly in 27% and vestibular anomaly in 16.2%., Conclusion: Some of the classical etiologies of SD were detected in our patient population, along with a high prevalence of size or morphological anomalies of the bony labyrinth, diagnosed in most cases from systematic measurements from CT images. In time, MRI should also allow detection of these abnormalities and diagnosis of lesions currently not detectable on MRI.

Leptomeningeal meningitis occurs in approximately 5% of metastatic breast cancers, and there is no standard treatment for this complication. We retrospectively analyzed the clinical data and cerebrospinal fluid of 24 patients treated with high-dose intrathecal methotrexate for breast cancer leptomeningeal meningitis (BLM). Cytologic response (CSF cytology without neoplastic cells after treatment) was observed in 11 patients (46%) and related to survival (P = 0.005). In addition, clinical symptoms improved in all 11 patients who had a cytologic response and in 7 patients (54%) without cytologic response (P = 0.02). The predictive value of cytologic response needs further confirmation. Cytologic response could be helpful in the management of intrathecal chemotherapy in patients with BLM.

This clinical report illustrates the usefulness of routine CA 15.3 assay during the follow-up of patients treated for invasive breast cancer. This patient presented an isolated elevation of CA 15.3 eighteen months after initial treatment of inflammatory breast cancer. The scientific committee for breast cancer decided to modify the hormonotherapy, even without clinical or radiological event (tomodensitometry, echography, scintigraphy). The prompt CA 15.3 normalization persisted for more than seven years. When CA 15.3 levels increased again, a positron emission tomodensitometry was performed and revealed pulmonary nodes. The sole modification of hormone treatment, based upon isolated increase of CA 15.3, led to seven years of clinical and biological stability for our patient with probable pulmonary metastases.

The aim of this study is to appreciate the incidence of patients with isolated conductive hearing loss with normal drum due to superior semicircular canal dehiscence (SCD). It is a prospective radiological study. Two hundred and seventy-two patients with a normal drum suffering from isolated unilateral or bilateral conductive or mixed hearing loss were included in a prospective radiological study. A high resolution computerized tomography (HRCT) was performed in all the patients. Those who were found to have a unilateral or bilateral SCD underwent further etiological, clinical, audiologic evaluation. Ten patients with conductive or mixed hearing loss were found to have a unilateral or bilateral SCD. The disease was bilateral in five cases, and most often associated with a dehiscence of the tegmen tympani on both sides, supporting the theory of the congenital nature of the disease. There was no clear correlation between symptoms and the size of the SCD. Because patients were not suffering from incapacitating vestibular symptoms, they were not operated for surgical occlusion of the SCD, and were referred to a hearing aid specialist to improve hearing. Conductive or mixed hearing loss due to SCD is relatively frequent, justifying in our opinion that a systematic HRCT be carried out before surgery of any patient with conductive hearing loss.

Purpose: at our institution, CA 15-3 assays are routinely used for the early diagnosis of recurrence during the follow-up of patients treated for breast cancer, although published guidelines do not recommend this procedure. So, we decided to totally re-assess the usefulness of this policy., Patients and Methods: all records of patients presenting a first recurrence, local (50 cases) or metastatic (88 cases), of breast cancer during 2003 were re-examined. An increase in CA 15-3 concentration of more than 25% was considered significant., Results: an increase was observed in 18% of non metastatic recurrences. These increases had a prognostic value. CA 15-3 levels remained stable in 23% of metastasis cases and increased in 77%. In 14% of cases, the increase in CA 15-3 levels confirmed a clinically or radiologically suspected metastasis. Moreover, increased CA 15-3 levels in the absence of suggestive clinical or radiological signs led to the diagnosis in 18% of metastasis, 50% of which involved the bone., Conclusion: our study demonstrates that CA 15-3 is useful for the early diagnosis of recurrence. Eighteen per cent of metastases were diagnosed by a marker increase alone. CA 15-3 assays could be useful in the early management of these metastases in patients treated for breast cancer.

CXC chemokine receptor 4 (CXCR4) has been reported to be involved in organ-specific homing of breast cancer-derived metastasis. We investigated CXCR4 expression by immunohistochemistry as a possible new prognostic factor for primary breast cancer. Two groups of women treated for breast cancer in 1991 at the Centre for the fight against cancer of Upper Normandy-France (Centre de Lutte contre le Cancer de Haute Normandie) were assessed retrospectively. CXCR4 expression was evaluated using standard immunohistochemistry. Usual prognostic factors were recorded in the computer database. Final date of follow-up was December 31, 2001. Tissues were available for 110 node-positive and 84 node-negative breast cancer patients treated in 1991. CXCR4 membrane staining was considered a strong prognostic factor for both 10-year metastasis-free- (p < 0.0001) and overall survival (p < 0.0001) in node-negative but not in node-positive breast cancer patients. CXCR4 cytoplasmic staining was not considered a significant prognostic factor. Our results suggest that CXCR4 membrane staining could be considered a new prognostic factor. Moreover, targeting CXCR4 in primary breast cancer patients may be a new therapeutic concept. However, these results warrant further investigation.

Background and Purpose: The purpose of our study has been to describe the pre-operatively MR Imaging appearance of masses in the parotid gland which may be sources of clinical and radiological confusion., Methods: Sixty-eight adults patients with a parotid mass (39 female, 29 male) has been prospectively investigated. T1-weighted, T2-weighted, diffusion-weighted and contrast-enhanced dynamic MR images were performed by using a 1.5 or 1 T MR Imaging unit (Philips Gyroscan Intera 1.5 T. Siemens Expert 1 T). All patients underwent a parotidectomy with histopathologic analysis., Results-Conclusions: In case of pleomorphic adenoma (N=30) MR imaging sensibility, specificity and accuracy were respectively 87.5, 80.5 and 83%. In case of Warthin tumors (N=13) the same values were respectively 45.5, 93 and 85%. In case of malignant tumors (N=13) theses values were respectively 71, 89 and 87%. Our routine MR Imaging study appears excellent not only for assessing the type and extent of benign salivary gland tumors and the relationship to adjacent structures, but also for determining whether the tumor is benign or malignant.

Background: The authors evaluated the long-term efficacy and side effects in patients with nonmetastatic, unilateral, inflammatory breast cancer (IBC) who received homogeneous treatment with intensive induction chemotherapy followed by a maintenance regimen., Methods: One hundred twenty patients were randomized to receive high-dose fluorouracil, epirubicin, and cyclophosphamide (FEC-HD) (fluorouracil 750 mg/m(2) on Days 1 to 4, epirubicin 35 mg/m(2) on Days 2 to 4, and cyclophosphamide 400 mg/m(2) on Days 2 to 4 for 4 cycles every 21 days) with or without lenograstim. Locoregional treatment consisted of surgery and/or radiotherapy. Maintenance chemotherapy was FEC 75 (fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) on Day 1 every 21 days for 4 cycles). No hormone treatment was allowed., Results: The safety of the FEC-HD regimen was described previously. Among 102 patients who underwent surgery, a pathologic complete response (pCR) was achieved by 23.5% of patients with breast tumors and by 31.4% of patients with involved axillary lymph nodes. The overall pCR rate was 14.7%. One hundred nine patients received FEC 75. After a median 10 years of follow-up, the disease-free survival (DFS) and overall survival (OS) rates were 35.7% and 41.2%, respectively. The median DFS was 39 months (95% confidence interval [95% CI], 25-53 months), and the median survival was 61 months (95% CI, 43-79 months). Five patients developed a temporary decrease in left ventricular ejection fraction without congestive heart failure. In the lenograstim group, 1 patient developed acute myeloblastic leukemia M2, and 1 patient developed myelodysplastic syndrome., Conclusions: FEC-HD induction chemotherapy followed by FEC 75 maintenance regimen had moderate and acute long-term toxicities and lead to high DFS and OS rates in patients with IBC., ((c) 2006 American Cancer Society.)

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.

Background: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was shown previously that a delay in the initiation of RT resulted in a higher local recurrence (LR) rate. In the current retrospective analysis, the authors investigated whether the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC., Methods: Among 7 French Adjuvant Study Group trials, 1831 patients were assessable, including 475 patients who received RT directly after BCS (95 patients received no adjuvant therapy, and 380 patients received hormone therapy), 567 patients who received RT after the third chemotherapy (CT) cycle (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and 789 patients received RT after the sixth CT cycle. In the 1356 patients who received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50 mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of patients., Results: After a median follow-up of 102 months, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02). Patients who received hormone therapy were less likely to develop LR (P = 0.02). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic factors., Conclusions: In the study population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormone therapy. The number of CT courses could modified this risk.

Objective: To describe different sequences on magnetic resonance imaging (MRI) in otosclerosis with peri-cochlear involvement., Method: MRI T1 and T2 sequences with T1 gadolinium injection and computed tomography (CT) scans with millimetric slices on axial and coronal views were obtained. The diagnosis of bilateral otosclerosis was confirmed by surgical exploration., Results: On the CT scan, there was a fourth turn of the cochlea which appeared on the MRI T1 sequence with an intermediate signal and on the T2 sequences with a high intensity signal. After gadolinium injection, there was signal enhancement, suggestive of active otospongiosis. On the CT scan, there was another lesion in front of the cochlea with endosteal involvement. This was no however visible on the MRI, even after gadolinium infusion, in accordance with inactive otospongiosis., Discussion: We reviewed the literature concerning MRI and results in otosclerosis., Conclusion: MRI of the labyrinth with T1 sequences and gadolinium injection can be contributive to the diagnosis of otosclerosis to differentiate inactive from inactive otospongiosis. However, prospective studies must be conducted to confirm this hypothesis.

Margin status is regarded as a major prognostic factor for local recurrence after breast conservative treatment. Margin definition in the literature is not always clear and precise. The impact on the therapeutic management may be quite different. This paper presents the radiotherapeutic attitude according to a survey realized in the twenty French cancer centers. The surgical practice in terms of margins status is appraised. The radiotherapist attitude in terms of boost's modulation is specified.

PURPOSE To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 50) or the same regimen with epirubicin 100 mg/m(2) (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group-05 trial. PATIENTS AND METHODS One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. CONCLUSION After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection., (Copyright 2004 American Society of Clinical Onocology)

Objective: The purpose of this study was to assess the value of virtual endoscopy (VE) in the diagnosis of lesions of the ossicular chain and to compare virtual endoscopy and two-dimensional (2D) spiral computed tomography (CT) data., Study Design: Retrospective study., Setting: A university hospital., Patients: Fifty-eight patients with suspected ossicular chain lesions underwent a high-resolution CT of the temporal bone with both 2D data and VE before surgery., Main Outcome Measures: Two views were chosen for VE. The CT data obtained (2D, VE, and both 2D and VE) were compared with the lesions noted during surgery., Results: In the diagnosis of dislocation of the ossicles or prostheses, VE seemed to be a better technique than 2D CT. Views chosen for the VE proved to be ineffective for diagnosing epitympanic fixations. VE was not adapted to the study of otosclerosis. We found it necessary to use the data provided by the addition to 2D CT data in the diagnosis of ossicular lysis and minor aplasia. Radiologic analysis of the lesions of the long process of the incus and the incudostapedial joint was improved by performing both 2D CT and VE. VE reconstruction of the stapes proved to be difficult, especially in cases of inflammation of the middle ear., Conclusion: This study demonstrates the value of VE in the diagnosis of dislocation of the ossicles and ossicular prostheses. VE was less effective in diagnosing other pathologies of the ossicular chain.

Background and Purpose: To replace digital subtraction angiography (DSA) in carotid stenosis evaluation, noninvasive imaging techniques have to reach a high concordance rate. Our purpose is to compare the concordance rates of contrast-enhanced MR angiography (CEMRA) and CT angiography (CTA) with Doppler ultrasound (DUS) in clinical routine practice., Methods: We evaluated prospectively with DUS, CEMRA, and CTA 150 patients suspected of carotid stenosis. The overall concordance rates of the 3 techniques were calculated for symptomatic stenosis > or =50% and > or =70%, for asymptomatic stenosis > or =60%, and for occlusion. For the carotid arteries treated by surgery (n=97), the results of each method and combined techniques were recorded, and misclassification rates were evaluated from surgical reports., Results: The overall concordance rates of DUS-CEMRA, DUS-CTA, and CEMRA-CTA were not statistically different. However, the concordance rate of DUS-CEMRA (92.53%) was significantly higher than that for DUS-CTA (79.10%) in the surgical asymptomatic stenosis group (P=0.0258). CTA considered alone would misclassify the stenosis in a significant number of cases (11 of 64) in the surgical asymptomatic group compared with CEMRA (3 of 67) and DUS (1 of 66) (P=0.0186 versus MRA, P=0.0020 versus DUS)., Conclusions: With the techniques as utilized in our study, the overall concordance rates of combined noninvasive methods are similar for measuring carotid stenosis in clinical routine practice, but in asymptomatic carotid stenosis, the decision making for surgery is significantly altered if DUS and CTA are considered in place of DUS and CEMRA.

Purpose: Our study consists of a comparison of traditional computed tomography (CT) data sets with 2 views of virtual endoscopy in the preoperative evaluation of various diseases of the middle ear., Materials and Methods: We studied 59 patients, all sent for conductive hearing loss with normal eardrum who underwent a complete CT examination: axial helical acquisition and coronal incremental acquisition: virtual endoscopy with selection of two reproducible views: an external one of the auditory canal and a lower one of the hypotympanum. Reading was performed by 2 independent radiologists. All patients were subsequently operated by the same surgeon. Results were compared with surgical reports., Result: Virtual endoscopy is valuable for the evaluation of ossicular and prosthesis dislocations, morphological anomalies of the malleus, incus, and stapes superstructure. Nevertheless, standard axial and coronal CT images remain necessary as confirmed by the poor results of virtual endoscopy in cases of attic obstruction, cholesteatomas and otospongiosis., Conclusion: Virtual endoscopy is a valuable technique of the evaluation of some ossicular chain pathologies but it cannot be used alone.

BACKGROUND: After radiological procedures, the incidence of acute renal failure varies greatly, and cholesterol embolism may not always be recognized. Little, if anything, is known about whether recommendations for the prevention of either complication are correctly implemented. METHODS: We performed a prospective epidemiological study in a large population (n=809) of consecutive inpatients in a university hospital. The patients were monitored for risk factors, ongoing medications, and details of preventive measures and of radiological procedures. Contrast nephropathy was defined as a 25% rise in serum creatinine. Cholesterol embolism was defined by the presence of two typical signs. We analyzed the incidence, risk factors, and prevention of contrast nephropathy and cholesterol embolism. RESULTS: The most frequent procedure that our patients underwent was cardiac angiography (50%). The incidence of contrast nephropathy was 7%. We confirmed the classical risk factors (diabetes, dose of contrast medium, and renal insufficiency) and added potentially nephrotoxic medications as an independent risk factor. Fluid therapy, commonly proposed in high-risk patients, was adequately carried out in only 12% of patients. The incidence of cholesterol embolism was 4%, with 10% renal involvement. Arteriosclerosis and renal insufficiency were risk factors, but anticoagulation therapy was not. CONCLUSION: Adequate fluid therapy and discontinuation of nephrotoxic medications should be more systematically implemented in the prevention of contrast nephropathy. Recognition of cholesterol embolism is crucial.

Objective: To assess the current place of embolization of the uterine arteries in the treatment of severe post-partum haemorrhages., Materials and Methods: A retrospective study of 13,160 deliveries in a level III maternity unit between January 1996 and December 2001. Five hundred and forty-nine post-partum haemorrhages were diagnosed. Seventeen (0.13%) patients had a haemorrhage which did not respond to treatment using obstetric manoeuvres and uterotonic drugs. Twelve patients aged between 19 and 34 years old benefited from embolization of the uterine arteries. Nine patients had delivered by Caesarian section and three vaginally. The aetiologies found were uterine atony (n=8), placenta praevia (n=1), placenta accreta (n=1), abruptio placentae (n=1) and uterine myomas (n=1)., Results: The success rate of embolization was 91.6%. One failure, resulting from cardiovascular shock during the procedure, led to the patient being transferred as an emergency to the operating theatre for a haemostasis hysterectomy. It was due to placenta increta. No maternal deaths were reported. No complications because of the technique used were noted. One patient successfully delivered, following a normal pregnancy, one year after embolization., Conclusion: Embolization of the uterine arteries is indicated in severe post-partum haemorrhage, irrespective of the aetiology or the type of delivery. It should be offered as soon as primary management measures undertaken for haemorrhage are judged as ineffective. Its place in the treatment strategy, is in all cases before embarking on surgery, which is the final recourse in the case of failure. It is a fairly uninvasive procedure, which preserves the potential for future pregnancies.

Objectives: This study was directed to evaluate the morphological and dynamic aspects of the pelvic floor muscles by the MRI in patients with gynecological prolapse before and after surgery., Materials and Method: MRI had been made before surgical repair in 13 patients with gynecological prolapse, in 9 of this group MRI had been made after the surgery and the group of control was formed by 4 healthy women. We had used morphologic sequences T2 (TSE) and T1 (SE) and fast sequences T2 (TSE) in different positions: at rest, straining and retention for describe and evaluate the anatomic modification of the levator ani and the changes observed after surgery., Results: The MRI is able to identify the changes of the levator ani muscles: intrinsic degeneratives lesions, increase of the muscular laxity especially for the puborectalis muscle and the wider of the levator hiatus. After surgical repair, the levator hiatus width and the laxity of the puborectalis muscle are slightly modified during straining., Conclusion: There are lesions in the muscular structure of the pelvic floor in patients with gynecological prolapse. The MRI was able to analyse these lesions very well especially after the use of fast sequences. The MRI is the future for exhaustive and non invasive study of the static pelvic disorders.

Intraductal papillary-mucinous tumor (IPMT) is defined as a syndrome consisting of dilatation of the main pancreatic duct and/or branch ducts associated with mucin overproduction. The purpose was to evaluate the usefulness of different imaging techniques (CT, EUS, ERCP) for determination of tumor invasion and pancreatic extension. Diagnosis often is delayed because it is confused with chronic pancreatitis or cystic neoplasms of the pancreas. It is difficult to rule out invasive malignancy. MRCP can be an essential imaging modality because it is a non-invasive technique. Intraductal ultrasound or pancreatoscopy could become in the future an additional useful preoperative procedure. A high frequency of invasive carcinoma in patients operated for pancreatic IPMT is observed. Surgical resection should be extended until a normal tissue margin is encountered.

Endovascular repair of abdominal aortic aneurysms (AAA) requires regular surveillance for early detection of endograft failure. CT scanning is the gold standard surveillance procedure. The purpose of this study was to assess the reliability of color duplex ultrasound (CDU) in comparison to CT scanning for detection of endoleaks and changes in aneurysmal diameter. From November 1996 to September 1999, a total of 41 patients treated by aortic endografting underwent regular surveillance with both CT scanning and CDU. There were 39 men and 2 women with a mean age of 71 years (range, 50-83). Endovascular treatment involved deployment of a straight aorto-aortic stent in 6 cases, bifurcated stent in 33, and aorta-to-unilateral iliac artery stent in 2. Stent deployment failed in one case; the procedure was conversion to open surgery. Primary or secondary endoleaks were detected in 17 patients (42%). Our findings indicated that CDU is less reliable than the CT scan for detection of endoleaks, but that reliability of CDU for surveillance of aneurysmal diameter is fair.

The authors report a case of right atrial angiosarcoma in a 29 year old man presenting with massive pericardial effusion. This case illustrates the value of MRI in the preoperative evaluation, providing accurate information about the site and extension of the tumor, and even about the malignant nature of the lesion. Multiplanar transesophageal echocardiography did not provide any additional information in this case.