Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study.

BACKGROUND: Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination. PATIENTS AND METHODS: This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively. RESULTS: From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601-0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case-control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672-0.813; 8.1 versus 6.4 months). CONCLUSIONS: In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC.

Port catheter versus peripherally inserted central catheter for postoperative chemotherapy in early breast cancer: a retrospective analysis of 448 patients.

PURPOSE: We aimed to compare the complication rate between port catheters (PC) and peripherally inserted central catheters (PICC) for the administration of postoperative chemotherapy for breast cancer. METHODS: All patients treated from January 2010 to August 2012 at the Centre Henri Becquerel for early breast cancer requiring postoperative chemotherapy were retrospectively screened. The primary endpoint was the occurrence of a major complication related to the central venous catheter. Major complications were defined as any grade 3 event according to CTCAE 4.0, delay in chemotherapy >7 days, change of the device, life-threatening event, event requiring a hospitalization, or a prolongation of hospitalization. RESULTS: A total of 448 patients were included; 290 had a PC and 158 a PICC. Overall, 31 major complications related to the central venous catheter were observed: 13 for patients with a PC (4.5%) and 18 for patients with a PICC (11.4%). In univariate analysis, having a PICC was the only factor significantly associated with a higher risk of major complications (HR = 2.83, p = 0.0027). We observed a trend for a higher risk of major complications for patients older than 60 years or with BMI >25 (p = 0.06). In multivariate analysis, having a PICC was the only predictive factor of major complications (HR = 2.89, p = 0.004). CONCLUSIONS: In univariate and multivariate analysis, having a PICC instead of a PC was the only predictive factor of device-related major complication. If confirmed prospectively by the NCT02095743 ongoing trial, this result might modify the management of adjuvant chemotherapy administration.

Cholesterol granuloma of the middle ear invading the cochlea.

OBJECTIVES: To report a second case of cholesterol granuloma of the middle ear invading the cochlea. MATERIAL AND METHODS: A 54-year-old woman, who had undergone right-side tympanoplasty with stapedectomy, complained of intermittent right-side otorrhea associated with cophosis. Otomicroscopy found anterior eardrum perforation with mucopurulent effusion. Computed tomography (CT) showed a lesion filling the tympanic cavity, exposing the tympanic facial nerve, with destruction of the ossicles; the vestibule and cochlea were ossified except for the basal turn. The petrous apex was normal. Magnetic resonance imaging (MRI) showed invasion of the cavity and basal turn of the cochlea by a mass in heterogeneous hypersignal on T-1 weighted images, non-enhanced by gadolinium injection, and hyperintensity on T2-weighted images. Cholesterol granuloma of the middle ear was suspected, with surgery indicated due to the facial nerve exposure and cochlear invasion. RESULTS: A brownish-yellow compressive mass invading the basal turn of the cochlea, suggestive of cholesterol granuloma, was removed. Histologic examination confirmed diagnosis. CONCLUSION: Direct invasion of the otic capsule by cholesterol granuloma is extremely unusual. Surgery is indicated in such cases, to avoid onset of neurologic complications.

[Computed tomography of the normal and pathologic temporal bone]. / Anatomie tomodensitométrique de l'oreille normale et malformée.

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.

High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer.

BACKGROUND: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS: Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis. RESULTS: In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%). CONCLUSION: Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.

[MR spectroscopy of the prostate with external surface coils: clinical feasibility]. / Spectro-IRM de prostate avec antennes externes: faisabilité en pratique clinique?

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.

Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy.

BACKGROUND: We investigated whether circulating tumor cells (CTCs) and circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy combined with bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: In a French substudy of the MO19391 trial, CTC and CEC counts (CellSearch system) at baseline and changes after two cycles of treatment were correlated with time to progression (TtP). RESULTS: CTC and CEC levels were not correlated in the 67 patients included. At baseline, CTC positivity was a significant prognostic marker for TtP at a threshold of 3 CTC/7.5 ml (P < 0.05) but not at 5 CTC/7.5 ml (P = 0.09). Baseline CEC levels (median 17 CEC/4 ml, range 1-769) were associated with age > or =45 years (P = 0.01), elevated lactate dehydrogenase (P < 0.01) and not with TtP at any threshold. Changes of CTC count during treatment were not a surrogate of TtP, with any of the model tested (threshold based or relative decrease in percent). However, increase in CEC count was associated with improved TtP, at the threshold of 20 CEC/4 ml (P < 0.01). CONCLUSION: Bevacizumab combined with first-line chemotherapy may modify the predictive value of CTC during treatment possibly due to impaired tumor cells intravasation through vessels endothelium. Variations in CEC levels appear to be a promising early surrogate marker of TtP under antiangiogenic treatment.

[Sudden deafness: value of imaging. Results from a prospective study of 37 patients]. / Surdités brusques: intérêt de l'imagerie. A propos d'une étude prospective de 37 cas.

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.

[Usefulness of CA 15-3 for ten years follow-up of a patient with invasive breast cancer]. / Apport du CA 15.3 dans la prise en charge sur plus de 10 ans d'une patiente atteinte d'un cancer du sein invasif.

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.

[Routine use of serial plasmatic CA 15-3 determinations during the follow-up of patients treated for breast cancer. Evaluation as factor of early diagnosis of recurrence]. / Utilisation en routine du CA 15.3 dans la surveillance des patientes traitées pour un cancer du sein invasif. Impact en termes de diagnostic précoce de récidive.

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.

[Parotid gland masses: diagnostic value of MR imaging with histopathologic correlations]. / Morphologie IRM des tuméfactions de la glande parotide. Corrélations histopathologiques.

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.

Epirubicin-vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial.

The aim of the study was to compare our reference adjuvant chemotherapy, FEC100 (fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2) and cyclophosphamide 500 mg m(-2), six cycles every 21 days), to an epirubicin-vinorelbine (Epi-Vnr) combination for early, poor-prognosis breast cancer patients. Patients (482) were randomised to receive FEC100, or Epi-Vnr (epirubicin 50 mg m(-2) day 1 and vinorelbine 25 mg m(-2), days 1 and 8, six cycles every 21 days). The 7-year disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and 88.9% with Epi-Vnr. There were significantly more grades 3-4 neutropenia (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P<0.0001), stomatitis (P=0.0007) and alopecia (P<0.0001) with FEC100. No cases of congestive heart failure were reported, whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr. One case of acute myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow-up, there was no difference between treatment arms. Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients, and could be an alternative to FEC100, taking into account respective safety profiles of both regimens.

[Surgical and radiotherapeutic approaches according to postoperative margins analysis in breast cancer: survey realized in 20 French cancer centers]. / Attitudes chirurgicales et radiothérapiques en fonction de l'analyse des berges-marges dans les tumeurs mammaires: enquête réalisée auprès de 20 centres de lutte contre le cancer.

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.

[Cochlear otosclerosis and pseudo fourth turn of the cochlea]. / Otospongiose cochléaire et pseudo-quatrième tour de cochlée.

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.

[Advantage of virtual endoscopy in the evaluation of the ossicular chain]. / Intérêt de l'endoscopie virtuelle dans l'exploration de la chaîne ossiculaire.

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.

[Imaging of intraductal papillary mucinous tumor of the pancreas: literature review]. / Imagerie des tumeurs intracanalaires papillaires mucineuses du pancréas: revue de la littérature.

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.

Comparison of color duplex ultrasound and computed tomography scan for surveillance after aortic endografting.

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.

[Contribution of pelvic floor MRI in the morphological and functional analysis of pre and postoperative levator muscle in patients with genital prolapse]. / Apport de l'IRM du plancher pelvien dans l'analyse morphologique et fonctionnelle du muscle releveur en pré et postopératoire chez des patientes présentant un prolapsus génital.

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.