Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS.

PURPOSE: We evaluated the addition of breast magnetic resonance imaging (MRI) to standard radiologic evaluation on the re-intervention rate in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery. PATIENTS AND METHODS: Women with biopsy-proven DCIS corresponding to a unifocal microcalcification cluster or a mass less than 30 mm were randomly assigned to undergo MRI or standard evaluation. The primary end point was the re-intervention rate for positive or close margins (< 2 mm) in the 6 months after randomization ( ClinicalTrials.gov identifier: NCT01112254). RESULTS: A total of 360 patients from 10 hospitals in France were included in the study. Of the 352 analyzable patients, 178 were randomly assigned to the MRI arm, and 174 were assigned to the control arm. In the intent-to-treat analysis, 82 of 345 patients with the assessable end point were reoperated for positive or close margins within 6 months, resulting in a re-intervention rate of 20% (35 of 173) in the MRI arm and 27% (47 of 172) in the control arm. The absolute difference of 7% (95% CI, -2% to 16%) corresponded to a relative reduction of 26% (stratified odds ratio, 0.68; 95% CI, 0.41 to 1.1; P = .13). When considering only the per-protocol population with an assessable end point, the difference was 9% (stratified odds ratio, 0.59; 95% CI, 0.35 to 1.0; P = .05). Total mastectomy rates were 18% (31 of 176) in the MRI arm and 17% (30 of 173) in the control arm (stratified P = .93). For 100 lesions seen on MRI, nonmass-like enhancement was more predominant (82%) than mass enhancement (20%). Nevertheless, no specific morphologic and kinetic parameters for DCIS were identified. CONCLUSION: The study did not show sufficient surgical improvement with the use of preoperative MRI to be clinically relevant in DCIS staging. However, this could be reconsidered with the improvement of new MRI sequences and new modalities in magnetic resonance techniques.

Activity of cabozantinib in radioresistant brain metastases from renal cell carcinoma: two case reports.

BACKGROUND: Renal cell carcinoma represents 3-5% of adult malignant tumors. Metastases are found in 30-40% of patients and brain metastases occurred in more than 10% of them. Despite significant progress in medical treatment, patients with brain metastases still have a limited survival. Cabozantinib, a tyrosine kinase inhibitor directed against vascular endothelial growth factor receptors, was recently registered for the treatment of metastatic renal cell carcinoma. Almost no data are, however, available on patients with brain metastases. CASE PRESENTATION: Case 1 is a 51-year-old man of North African origin; Case 2 is a 55-year-old European man. Case 1 and Case 2 had metastases of renal carcinoma at initial diagnosis and were treated with vascular endothelial growth factor receptors tyrosine kinase inhibitors. Case 1 had clear cell renal carcinoma and underwent nephrectomy; he then received several lines of tyrosine kinase inhibitor directed against vascular endothelial growth factor receptors and the mTor complex. During the second treatment a brain metastasis was diagnosed and treated with radiosurgery with rapid efficacy. Two years later he received nivolumab, an antibody directed against the programmed death-1 and programmed death-ligand 1 complex, but disease progression was observed with the reappearance of the brain metastasis together with neurologic symptoms. Cabozantinib was administered and induced a rapid clinical improvement as well as tumor regression in all sites including his brain. Sequencing of his tumor evidenced a mutation of the MET gene. Case 2 had a papillary renal carcinoma with brain metastases at time of diagnosis. After radiation of the brain tumors, a vascular endothelial growth factor receptor tyrosine kinase inhibitor was administered for 3 years. The disease was under control in all sites except in his brain; several new brain metastases requiring new radiation treatments developed. The disease finally progressed at all metastatic sites including his brain and he had several neurological symptoms. Cabozantinib was administered and rapidly induced a clinical improvement; a further computed tomography scan and brain magnetic resonance imaging showed significant tumor regressions. No MET gene mutation or amplification was observed in the tumor analysis. CONCLUSIONS: These case reports indicate that cabozantinib was able, first, to reach brain tumors and second, to induce significant regressions in renal carcinoma brain metastases that were resistant to radiation as well as to previous systemic vascular endothelial growth factor receptor tyrosine kinase inhibitors.

Editorial on "What is a potentially damaging vaccination delay in children younger than 2 years?"

Control of hepatitis B through routine infant immunization in more than 95% of countries has reduced the prevalence of chronic hepatitis carriers to less than 1%-2% in immunized cohorts of children even in high endemicity countries. In that context the authors of this editorial found the results of a paper by Gras et al in this issue concerning. They performed a Delphi survey of 37 French immunization experts and the results concluded that delayed hepatitis B immunization would cause "potential damage" only after 11 years. Large cohorts of French children and adolescents remain susceptible to hepatitis B infection. Given the high rates of immigration to France from areas of higher endemicity, the higher birth rate and degree of integration of these groups into the health system, plus the lower age of sexual debut and the use of injectable drugs in the general population, we cannot agree that a delay of 11 years is acceptable. Rates of adolescent immunization are quite low so relying on protection at this age will yield little in terms of population protection. Loss of confidence in Hepatitis B vaccine following disproved allegations that the vaccine caused Multiple Sclerosis persists in France, and we believe the results of this paper sends a damaging message to health workers and parents in France and beyond.

[BCG in Europe in 2004]. / Le BCG en Europe en 2004.

BCG immunization policies are somewhat uniform in eastern Europe. The incidence rates of tuberculosis are already very high, and are increasing. WHO recommendations, ie. BCG immunization by intradermal injection at birth or as soon as possible after birth are implemented. In western countries, the incidence rates of tuberculosis are not clearly related to the local immunization policy. Some countries still immunize all children at birth or later, while others only immunize at-risk groups. The definition of the risk also differs from one country to another Finally, some countries do not offer immunization at all. The reasons for these disparities are examined, together with their implications for future French policy

Management of patients diagnosed with atypical ductal hyperplasia by vacuum-assisted core biopsy: a prospective assessment of the guidelines used at our institution.

BACKGROUND: Because of underestimation, surgical excision is recommended for atypical ductal hyperplasia diagnosed on directional vacuum-assisted biopsies. The following guidelines have been established according to our retrospective study published in 2008: excision for lesions ≥ 21 mm, follow-up for lesions <6 mm with complete removal of microcalcifications, and follow-up or excision for 6 to 21-mm lesions with respectively less or >2 atypical ductal hyperplasia foci. METHODS AND RESULTS: These guidelines were assessed in a prospective series of 124 patients with a median follow-up of 30 months. Conformity rate was 92%. Upgrading was 28% (15 of 53 patients) for conformed surgery and absent for surgery performed beyond the scope of guidelines. For the patients with benign result at surgery (n = 38) or just followed (n = 61), 3 cancers occurred in either breast at 1 to 3 years. CONCLUSIONS: These convenient guidelines can safely spare surgery for a subset of patients. However, annual mammographic follow-up is recommended since the risk of subsequent cancer remains high for both breasts.

Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization.

PURPOSE: Medical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre. METHODS: Both tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage. RESULTS: Committees' specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86). CONCLUSIONS: The present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies' characteristics, they can promote a collective and multidisciplinary approach to oncology.

Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? A retrospective study of 300 patients.

BACKGROUND: Atypical ductal hyperplasia (ADH) is diagnosed in 4% to 10% of directional vacuum-assisted stereotactic biopsies (DVABs) performed for microcalcifications. Since the underestimation rate varies from 7% to 36%, surgical excision is still recommended, although some authors have tried to identify a subset of patients who can be spared surgery. METHODS AND RESULTS: In this study, we analyzed a retrospective series of 300 patients with ADH on 11-gauge DVAB. The only 4 events that occurred (3%) in 135 of 184 patients (61%) who were followed may not be due to underestimation. Comparing the diagnoses on DVAB and surgical excisions for 116 patients (39%), we identified 3 subsets of patients: no underestimation (size <6 mm and complete removal), low rate of 4% (< or =2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm), and high rate of 36% to 38% (>2 foci ADH in microcalcifications either <6 mm with incomplete removal or > or =6 mm and <21 mm, lesion size > or =21 mm). CONCLUSIONS: Our results suggest that strict follow-up can be a safe option for the first 2 groups of patients, but that surgical excision is mandatory for patients from the third group.