Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force.

BACKGROUND: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. PATIENTS AND METHODS: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. RESULTS: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. CONCLUSIONS: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.

Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry).

The debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach's outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990-2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study's criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.

Evolution of older patients diagnosed with early breast cancer in Spain between 1998 and 2001 included in El Alamo III project.

INTRODUCTION: An increase in the number of cancer cases is expected in the near future. Breast cancer (BC) mortality rates increase with age even when adjusted for other variables. Here we analyzed BC disease-free survival (BCDFS) and BC specific survival (BCSS) in the El Alamo III BC registry of GEICAM Spanish Breast Cancer Group. MATERIALS AND METHODS: El Alamo III is a retrospective registry of BC patients diagnosed between 1998 and 2001. Patients with stage I-III invasive BC of age groups 55-64 years (y), 70-74 years and ≥ 75 years were included. Patients and tumors characteristics, treatments and recurrences and deaths were analyzed. RESULTS: 4343 patients were included within the following age intervals: 2288 (55-64 years), 960 (70-74 years), and 1095 (≥ 75 years). Older patients (≥ 70 years) were diagnosed with more advanced tumors (stage III) than younger patients (21.5% versus 13.4%, p < 0.0001). Mastectomies were performed more on older patients and they received less chemotherapy than younger patients (66.6% versus 43.1%, p < 0.00001 and 30.8% versus 71.6%, p < 0.0001, respectively). With a median follow-up of 5.9 years, 17.7% patients had BCDFS events in the younger group and 19.8% in the older group (p < 0.0001). A decrease in BCSS was also observed in older patients, either when analyzing patients ≥ 70y (p < 0.0001) and when differentiating by the two older groups (p < 0.0001). CONCLUSIONS: Our study suggests that older BC patients have worse outcomes what can be a consequence of receiving inadequate adjuvant treatments. Specific trials for these patients are warranted to allow us to treat them with the same scientific rigor than younger patients.

Phase I clinical trial of nintedanib plus paclitaxel in early HER-2-negative breast cancer (CNIO-BR-01-2010/GEICAM-2010-10 study).

INTRODUCTION: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. METHODS: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). RESULTS: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was ∼100%. The pathologic complete response was 50%. CONCLUSIONS: The combination allows the delivery of full-dose intensity, while efficacy seems promising.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

[Patients' opinions and expectations about the dialysis care process]. / Análisis de calidad percibida y expectativas de pacientes en el proceso asistencial de diálisis.

BACKGROUND: To determine the experiences and needs of patients on dialysis, in order to identify critical points of the care process and develop proposals for improvement. METHODS: Qualitative study using semistructured interviews with 22 patients on hemodialysis and peritoneal dialysis, from the Andalusian Health Service. Discourse analysis, using the SERVQUAL model. Triangulation of results. RESULTS: The diagnostic stage is described as the hardest moment as it requires acceptance of the disease. During hemodialysis, we see both positive adaptation and the perception of a diminished quality of life. The technique of peritoneal dialysis is evaluated positively, enabling greater independence, despite requiring more responsibility for self care. The contact with patients' organizations or the provision of a counseling service are valued as an aid in the process. With respect to different dimensions of the SERVQUAL model, human treatment and professional competence are valued. The critical points are lack of coordination, malfunctioning of transportation and lack of transparency in the management of waiting lists. Shortcomings in dealing with informal caregivers and the level of knowledge of professionals from areas other than Nephrology, also appear as deficiencies. CONCLUSIONS: The main proposals for improving the dialysis process are: attention to psychosocial aspects, the improvement of organizational aspects such as transport, and greater attention to informal caregivers.

Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study.

BACKGROUND: In order to determine the feasibility of substituting pegylated liposomal doxorubicin (PLD) for doxorubicin in combination with cyclophosphamide and trastuzumab as adjuvant therapy, we conducted a phase II study of the combination as first-line therapy in human epidermal growth factor receptor 2 (HER2) overexpressing metastatic breast cancer (MBC). METHODS: PLD 50 mg/m(2) and cyclophosphamide 600 mg/m(2) were administered every 4 weeks for six cycles; trastuzumab (4 mg/kg loading dose, then 2 mg/kg) was administered weekly for 24 weeks. The primary end point was objective response rate (ORR), and the secondary end points included time to progression (TTP), overall survival (OS), and safety. RESULTS: Among the 48 evaluable patients, ORR was 68.8% [95% confidence interval (CI) 55.69% to 81.91%], with 6 patients (12.5%) achieving a complete response and 27 (56.2%) a partial response. The median TTP was 12 months (95% CI 9-15.1 months), and the median OS was 34.2 months (95% CI 27.2-41.2 months). Febrile neutropenia was seen in three patients, grade 3 hand-foot syndrome in 29.2% of patients, and grade 3-4 mucositis in 22.9% of patients. Symptomatic congestive heart failure was not observed, and 16.7% of patients experienced grade 2 asymptomatic left ventricular systolic dysfunction. CONCLUSION: The combination of PLD-cyclophosphamide-concurrent trastuzumab is a feasible, safe, and effective first-line regimen for HER2-overexpressing MBC.

[Prevalence of antiretroviral drug genotypic resistance among HIV patients in Cuenca, Spain]. / Prevalencia de la resistencia genotípica a los fármacos antirretrovirales en pacientes VIH positivos en la provincia de Cuenca.

The aims were to assess the prevalence of resistances to antiretroviral drugs in HIV patients in the province of Cuenca and to determine the most frequently detected primary resistances. A total of 79 samples collected from April 2000 to July 2004 were analyzed. Resistance was detected using the genotypic technique VERSANTTM HIV1 (LiPA). Mutations more frequently found were M184V in the reverse transcriptase gene and V82A in the protease gene. The prevalence of primary resistances was 39.4%. Mutations more frequently detected were similar to those reported by other authors. The rate of primary resistance was higher than those found by other authors in Spain.

Effect of Sr content on the crystal structure and electrical properties of the system La2-xSrxNiO4+delta (0

Materials formulated as La(2-x)Sr(x)NiO(4+delta) (0

[Dietary behavior disorders: opinions and expectancies on prevention and treatment strategies from the perspective of the several social actors]. / Trastornos de la conducta alimentaria: opiniones y expectativas sobre estrategias de prevención y tratamiento desde la perspectiva de diferentes actores sociales.

AIMS: The prevalence increase of Eating Disorders in the last decades emphasizes the necessity to develop strategies from the public healthcare system which include the perspective of the principal implicated social actors. The present study aims to know their opinions and expectations regarding the prevention and treatment of Eating Disorders. METHODS: Realization of 5 focus groups (with relatives, adolescents, professionals from the health and educational sector, representatives from institutions and support groups) and 14 semi-structured interviews (with Eating Disorder patients and relatives) about strengths and weaknesses of actual prevention and treatment programs, expectations of change and suggestions for improvement. Analysis of contents and triangulation of results. RESULTS: The absence of resources and knowledge about Eating Disorders, the scarcity of transversal programs and insufficient coordination were named as the main weaknesses whereas interdisciplinary pilot programs were positively valued. As principal demands, major endowment of human and material resources, increased coverage of specialized services, promotion of specific training and improvement of coordination was asked for. Regarding prevention, preference toward an unspecific approach to the subject in order to hinder imitation between young people was highlighted. The care in Day Hospitals was considered one of the most appropriate treatment modalities for the characteristics of this disease being valued the potentially therapeutic effect of contact between Eating Disorder patients. The support network, the education field and the family were named as other important pillars in a multidisciplinary approach to the disease. There was also a demand for the development of combined programs. CONCLUSIONS: The discussion of different psychotherapeutic approaches, the role of support groups in the caring network as well as the post-hospital follow-up were identified as issues open to future research.