Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

<p>Abstract</p> <p>Background</p> <p>To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC).</p> <p>Methods</p> <p>We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated.</p> <p>Results</p> <p>The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83).</p> <p>Conclusions</p> <p>In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.</p

Faut-il opérer toutes les lésions de métaplasies cylindriques atypiques diagnostiquées sur macrobiopsie assistée par aspiration (A propos de 271 cas)

La métaplasie cylindrique atypique (MCA) fait partie des lésions frontières. Elle a eu de nombreuses descriptions et définitions au cours des années, et correspondrait à un stade précoce dans le développement de certains carcinomes in situ de bas grade et de certains cancers invasifs. Il n existe aucune recommandation actuelle sur sa prise en charge. Le but de notre étude va être de déterminer le taux de sous diagnostique et rechercher une sous-population qui pourrait bénéficier d'une surveillance. Nous avons donc réalisé, une étude rétrospective sur 271 cas de MCA issues de 5555 macrobiopsies par aspiration sur une période de 7 ans. Des critères cliniques (age, antécédent, statut ménopausique), radiologiques (Type d anomalie, taille, classification ACR), techniques (nombre de prélèvements, calibre de l'aiguille, qualité d'éxèrese de la lésion) et histologiques, ont été étudies afin de déterminer une corrélation entre ces facteurs et le risque de sous estimation.Nous avons retrouvés 128 MCA pures, 135 MCA+ hyperplasie canalaire atypique et 8 MCA+ hyperplasie lobulaire atypique. Il y a eu 184 patientes opérées et 46 surveillées. La chirurgie a retrouvé 34 cas de lésions plus sévères (23 carcinomes in situ, 7 cas de carcinomes invasifs et 4 cas mixtes). Ce qui fait un taux de sous diagnostique de 15 %.Seule la qualité d'exérèse de la lésion est statistiquement liée à ce risque.A la suite de nos résultats, nous avons tendance à proposer une chirurgie systématique en cas de MCA.The flat epithelial atypia (FEA) is part of the borderline tumors. She has had many definitions and descriptions over the years, and would correspond to an early stage in the development of some carcinomas in situ and some low-grade invasive cancers. There is no current recommendation on its management. The aim of our study will be to determine the rate of under diagnosis and seek a subpopulation that could benefit from monitoring. We have performed a retrospective study of 271 cases of MCA from 5555 stereotactic vacuum-assisted biopsies over a period of 7 years. Clinical criteria (age, history, menopausal status), radiological (type of radiological abnormality, size, ACR classification), technical (number of samples, size of the needle, quality of resection) and histology were are studying to determine a correlation between these factors and the risk of underestimation. We found 128 pure FEA, 135 FEA + atypical ductal hyperplasia and 8 FEA + atypical lobular hyperplasia. There were 184 patients operated and 46 monitored. Surgery has found 34 cases of more severe lesions (23 carcinoma in situ, 7 cases of invasive carcinoma and four mixed cases). This makes a rate of under diagnosis of 15%. Only the quality of resection of the lesion is statistically linked to this risk. In conclusion, we tend to propose a systematic surgery in cases of FEA.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

New methods for the quantification of mixed chimerism in transplantation

International audienceBackground Quantification of chimerism showing the proportion of the donor in a recipient is essential for the follow-up of hematopoietic stem cell transplantation but can also be useful to document an immune tolerance situation after solid organ transplantation. Historically, chimerism has been quantified from genomic DNA, but with technological advances, chimerism from donor-derived cell-free DNA seems particularly relevant in solid organ transplantation.Methods The reference method was until recently the short tandem repeat technique, but new innovative techniques as digital PCR (dPCR) and NGS, have revolutionized the quantification of chimerism, such as the so-called microchimerism analysis. After a short review of chimerism methods, a comparison of chimerism quantification data for two new digital PCR systems (QIAcuity™ dPCR (Qiagen ® ) and QuantStudio Absolute Q (ThermoFisher ® ) and two NGS-based chimerism quantification methods (AlloSeq HCT™ (CareDx ® ) and NGStrack™ (GenDX ® )) was performed.Results These new methods were correlated and concordant to routinely methods (r²=0.9978 and r²=0.9974 for dPCR methods, r²=0.9978 and r²=0.9988 for NGS methods), and had similar high performance (sensitivity, reproductibility, linearity).Conclusion Finally, the choice of the innovative method of chimerism within the laboratory does not depend on the analytical performances because they are similar but mainly on the amount of activity and the access to instruments and computer services

Early metabolic response of breast cancer to neoadjuvant endocrine therapy: Comparison to morphological and pathological response

International audienceBackground: Neoadjuvant endocrine therapy (NET) has shown efficacy in terms of clinical response and surgical outcome in postmenopausal patients with estrogen receptor-positive / HER2-negative breast cancer (ER+/HER2- BC) but monitoring of tumor response is challenging. The aim of the present study was to investigate the value of an early metabolic response compared to morphological and pathological responses in this population. Methods: This was an ancillary study of CARMINA 02, a phase II clinical trial evaluating side-by-side the efficacy of 4 to 6 months of anastrozole or fulvestrant. Positron Emission Tomography/Computed Tomography using 2-deoxy-2-[18F]fluoro-D-glucose (FDG-PET/CT) scans were performed at baseline (M0), early after 1 month of treatment (M1) and pre-operatively in 11 patients (74.2 yo ± 3.6). Patients were classified as early "metabolic responders" (mR) when the decrease of SUVmax was higher than 40%, and "metabolic non-responders" (mNR) otherwise. Early metabolic response was compared to morphological response (palpation, US and MRI), variation of Ki-67 index, pathological response according to the Sataloff classification and also to Preoperative Endocrine Prognostic Index (PEPI) score. It was also correlated with overall survival (OS) and recurrence-free survival (RFS). Results: Tumor size measured on US and on MRI was smaller in mR than mNR, with the highest statistically significant difference at M1 (p = 0.01 and 7.1 × 10- 5, respectively). No statistically significant difference in the variation of tumor size between M0 and M1 assessed on US or MRI was observed between mR and mNR. mR had a better clinical response: no progressive disease in mR vs 2 in mNR and 2 partial response in mR vs 1 partial response in mNR. One patient with a pre-operative complete metabolic response had the best pathological response. Pathological response did not show any statistically significant difference between mR and mNR. mR had better OS and RFS (Kaplan-Meier p = 0.08 and 0.06, respectively). All cancer-related events occurred in mNR: 3 patients died, 2 of them from progressive disease. Conclusions: FDG-PET/CT imaging could become a "surrogate marker" to monitor tumor response, especially as NET is a valuable treatment option in postmenopausal women with ER+/HER2- BC

Does evolution design robust food webs?

International audienceTheoretical works that use a dynamical approach to study the ability of ecological communities to resist perturbations are largely based on randomly generated ecosystem structures. In contrast, we propose here to asses the robustness of food webs drawn from ecological and evolutionary processes with the use of community evolution models. In a first part, with the use of Adaptive Dynamics theoretical framework, we generate a variety of diversified food webs by solely sampling different richness levels of the environment as a control parameter, and obtain networks that satisfactory compare with empirical data. This allows us to highlight the complex, structuring role of the environmental richness during the evolutionary emergence of food webs. In a second part, we study the short-term ecological responses of food webs to swift changes in their customary environmental richness condition. We reveal a strong link between the environmental conditions that attended food webs evolutionary constructions and their robustness to environmental perturbations. When focusing on emergent properties of our evolved food webs, especially con-nectance, we highlight results that seem to contradict the current paradigm. Among these food webs, the most connected appear to be the less robust to sudden depletion of the environmental richness that constituted their evolutionary environment. Otherwise, we appraise the "adapta-tion" of food webs, by examining how they perform after being suddently immersed in an environment of modified richness level, in comparison with a trophic network that experienced this latter environmental condition all along its evolution

Seamount effect on circulation and distribution of ocean taxa in the vicinity of La Pérouse, a shallow seamount in the southwestern Indian Ocean

International audienceThe La Pérouse seamount (60 m depth) has so far been poorly studied despite it being a short distance (160 km) from Réunion Island. As part of the MADRidge project, a multidisciplinary cruise was conducted to evaluate the effect of this shallow seamount on the local hydrology and ecology. Current measurements, temperature and chlorophyll-a profiles, and mesozooplankton and micronekton samples were collected between the summit and 35 km away. Micronekton data were supplemented with stomach content of pelagic top predators as well as fisheries statistics from the domestic longline fleet operating from Réunion. Vertical current profiles revealed distinct patterns between the offshore and seamount-flanked stations, giving evidence of topographical induced flow instabilities, notably on its leeward side (west) relative to the east flank. Distinct patterns in temperature and chlorophyll-a vertical profiles suggest the formation of convergent and divergent circulation cells as a result of the irregular and crescent-like summit topography. Spatial differences in zooplankton abundance were detected with higher biovolumes on the leeward flank. The overall acoustic backscatter for micronekton over the summit was weaker than offshore, but highly concentrated in the upper layer. Albacore tuna and swordfish dominate the longline catch west of Réunion, seemingly in association with a deep (900 m) topographic feature. Yet the largest catch is not directly associated with La Pérouse which would be too shallow for top predators to aggregate around in the long term. Enhanced levels of phytoplankton or zooplankton enrichment at La Pérouse were not demonstrated in this study, nor was there notable diversity of micronekton species. This might explain the relatively limited importance of this seamount to the tuna fisheries in this region

Gallium-68 and Copper-64 radiolabelling of hepatotropic GBVA10-9 or CPB peptide derivatives for hepatocellular carcinoma imaging

International audienc

A pre-operative score to discriminate fibroepithelial lesions of the breast: Phyllode tumor or fibroadenoma?

International audienceBackground/Aim: Fibroepithelial lesions (FEL) of the breast include fibroadenomas and phyllodes tumors (PT). Their histologic characteristics on core needle biopsy can overlap, while their clinical management is different. The aim of this study was to develop and to validate a pre-operative score for the diagnosis of PT with surgical decision rules. Patients and Methods: We developed a pre-operative score for the diagnosis of PT by performing logistic regression on 217 FEL of the Rene Huguenin Hospital. This score and the surgical decision rules were validated on 87 FEL of the Lariboisiere Hospital. Results: Three variables were independently and significantly associated with PT: Age ≤40 years, mammography's tumor size ≤3 cm and PT diagnosed by CNB. The pre-operative score was based on these three criteria with values ranging from 0 to 10. Surgical decision rules were created: The low-risk group of PT (score≥2) had a sensitivity of 92.6% and a LR-of 0.2, the high-risk group (score>7) had a specificity of 93.5% and a LR+ of 4.4. In the validation sample, surgical decision rules were applied. Conclusion: These surgical decision rules may prove useful in deciding which FEL needs surgical resection

Underestimation Rate at MR Imaging–guided Vacuum-assisted Breast Biopsy: A Multi-Institutional Retrospective Study of 1509 Breast Biopsies

International audiencePurpose To assess the rate of underestimation of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) at magnetic resonance (MR) imaging-guided vacuum-assisted breast biopsy and to explore the imaging, demographic, and histologic characteristics associated with lesion upgrade after surgery. Materials and Methods This retrospective study had institutional review board approval, and the need to obtain informed patient consent was waived. A total of 1509 MR imaging-guided vacuum-assisted biopsy procedures were performed in nine centers. A diagnosis of ADH was obtained after biopsy in 72 cases, and a diagnosis of DCIS was obtained in 118 cases. Pearson χ2 and Fisher tests were used to assess the association between demographic, MR imaging, and biopsy features and lesion upgrade. Univariate statistical analyses were performed, and each significant parameter was entered into a multivariate logistic regression analysis. Results Surgical excision was performed in 66 of the 72 ADH cases and in 117 of 118 DCIS cases. The ADH and DCIS underestimation rates were 25.8% (17 of 66) and 23.1% (27 of 117), respectively. Underestimation was 5.6-fold (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.7, 18.3) and 3.6-fold (OR = 3.6; 95% CI: 1.2, 10) more likely in mass (n = 20 for ADH and n = 20 for DCIS) than in non-mass (n = 46 for ADH and n = 97 for DCIS), compared with nonunderestimation, in ADH and DCIS respectively. At multivariate analysis, the use of a 9- or 10-gauge needle versus a 7- or 8-gauge needle was also an independently associated with underestimation when a diagnosis of ADH was made at MR imaging-guided biopsy. No other parameters were associated with of ADH or DCIS upgrade at surgery. Conclusion The rates of underestimation in ADH and DCIS diagnosed at MR imaging-guided vacuum-assisted biopsy were high, at around 25%, and were significantly associated with the presence of a mass at MR imaging. © RSNA, 2016

Quantitative CT Extent of Lung Damage in COVID-19 Pneumonia Is an Independent Risk Factor for Inpatient Mortality in a Population of Cancer Patients: A Prospective Study

International audienceBackground: CT lung extent has emerged as a potential risk factor of COVID-19 pneumonia severity with mainly semiquantitative assessment, and outcome was not assessed in the specific oncology setting. The main goal was to evaluate the prognostic role of quantitative assessment of the extent of lung damage for early mortality of patients with COVID-19 pneumonia in cancer patients. Methods: We prospectively included consecutive cancer patients with recent onset of COVID-19 pneumonia assessed by chest CT between March 15, 2020, and April 20, 2020, and followed until May 1, 2020. Demographic, clinical, laboratory test data and imaging findings were recorded. Quantitative chest CT assessment of COVID-19 pneumonia was based on the density distribution of lung lesions using a freely available software recently released (Myrian XP-Lung). The association between extent of lung damage and overall survival was studied by univariate and multivariate Cox analysis. The Uno C-index was used to assess the discriminatory value of the quantitative CT extent of lung damage. Results: Seventy cancer patients with chest CT evidence of COVID-19 were included. After a median follow-up of 25 days, 17 patients (24%) had died. The median quantitative chest CT extent of COVID-19 was 20% (IQR = 14–35, range = 3–59) for non-survivors vs. 10% (IQR = 6–15, range = 2–55) for survivors (p = 0.002). The extent of COVID-19 pneumonia was correlated with inpatient management (p = 0.003) and oxygen therapy requirements (p < 0.001). Independent factors associated with death were performance status (PS) ≥2 (HR = 3.9, 95% CI = [1.1–13.8] p = 0.04) and extent of COVID-19 pneumonia ≥30% (HR = 12.0, 95% CI = [2.2–64.4] p = 0.004). No differences were found regarding the histology of cancer, cancer stage, metastases sites, or type of oncologic treatment between the survivor and non-survivor groups. The cross-validated Uno C-index of the model including PS and extent of COVID-19 pneumonia was 0.83, 95% CI = [0.73–0.93]. Conclusions: The quantitative chest CT extent of COVID-19 pneumonia was a strong independent prognostic factor of early inpatient mortality in a population of cancer patients