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Atypical connectivity between brain regions and altered structure of the corpus callosum (CC) in imaging studies supports the long-distance hypoconnectivity hypothesis proposed for autism spectrum disorder (ASD). The aim of this study was to unveil the CC ultrastructural and cellular changes employing the valproic acid (VPA) rat model of ASD. Male Wistar rats were exposed to VPA (450 mg/kg i.p.) or saline (control) during gestation (embryonic day 10.5), and maturation, exploration, and social behavior were subsequently tested. Myelin content, ultrastructure, and oligodendroglial lineage were studied in the CC at post-natal days 15 (infant) and 36 (juvenile). As a functional outcome, brain metabolic activity was determined by positron emission tomography. Concomitantly with behavioral deficits in juvenile VPA rats, the CC showed reduced myelin basic protein, conserved total number of axons, reduced percentage of myelinated axons, and aberrant and less compact arrangements of myelin sheath ultrastructure. Mature oligodendrocytes decreased and oligodendrocyte precursors increased in the absence of astrogliosis or microgliosis. In medial prefrontal and somatosensory cortices of juvenile VPA rats, myelin ultrastructure and oligodendroglial lineage were preserved. VPA animals exhibited global brain hypometabolism and local hypermetabolism in brain regions relevant for ASD. In turn, the CC of infant VPA rats showed reduced myelin content but preserved oligodendroglial lineage. Our findings indicate that CC hypomyelination is established during infancy and prior to oligodendroglial pattern alterations, which suggests that axon-oligodendroglia communication could be compromised in VPA animals. Thus, CC hypomyelination may underlie white matter alterations and contribute to atypical patterns of connectivity and metabolism found in ASD.

Brain metastases (BM) occur in 15–35% of patients with metastatic breast cancer, conferring poor prognosis and impairing quality of life. Clinical scores have been developed to classify patients according to their prognosis. We aimed to check the utility of the Breast Graded Prognostic Assessment (B-GPA) and its modified version (mB-GPA) and compare them in routine clinical practice. This is an ambispective study including all patients with breast cancer BM treated in a single cancer comprehensive center. We analyzed the overall survival (OS) from BM diagnosis until death. The Kaplan–Meier method and Cox proportional hazard regression model were used in the analyses. ROC curves were performed to compare both scores. We included 169 patients; median age was 50 years. HER2-positive and triple negative patients were 33.7% and 20.7%, respectively. At the last follow-up, 90% of the patients had died. Median OS was 12 months (95% confidence interval 8.0–16.0 months). OS was worse in patients with > 3 BM and in patients with triple negative subtype. In our series, we confirm that B-GPA and mB-GPA scores correlated with prognosis. ROC curves showed that B-GPA and mB-GPA have similar prognostic capabilities, slightly in favor of mB-GPA.

Purpose:To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.Patients and Methods:PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2–4 prior lines of anti-HER2–based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes.Results:Seventy-one patients were recruited (n = 15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Regarding safety, grade 1–2 and 3–4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3–4 toxicities were neutropenia (66.4%) and thrombocytopenia (11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio = 0.40; P = 0.003).Conclusions:Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated ER-positive/HER2-positive advanced breast cancer with a PAM50 Luminal A or B subtype. The enrollment was stopped prematurely, and a new randomized cohort was opened in this population.

Introduction Benefit from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients with early breast cancer. The 21-gene recurrence-score (RS) assay (Oncotype DX, Genomic Health) is one gene-expression assay that provide prognostic and predictive information in hormone-receptor (RH) positive breast cancer. The results of the TAILORx study have confirmed that the majority of patients with tumors RH + and HER2 negative can avoid CT without increasing their risk of relapse. From 2012 to 2015 we used Mammaprint (MMP), in our institution and 60% of cases could avoided CT (communicated in SABCS 2015). Since 2017 we use RS for this purpose. Primary Objective To analyze the impact of using RS to change the indication of adjuvant CT. Secondary Objectives To analyze the association between different clinical pathological factors and the RS value, and calculate the difference between the cost of all RS test and the cost in direct expense of the treatment with CT of all patients who could avoid it thanks to the RS Material and methods We analyzed all RS test performed in the three ICO centers during 2017. We sent 112 tumor samples; in 2 samples adequated RNA for RS was not obtained. We compared the adjuvant treatment initially planned according to institutional treatment protocol with the treatment given after RS. We compared the direct economic costs of CT with the costs of the diagnostic test, and performed a logistic regression analysis of some pathological factors and RS value. Results The RS could be determined in 110 of 112 cases, in which there was indication of adjuvant CT. Only 14 patients received CT (12,72%) with the RS value, so CT was avoided in 96 patients (87,28%). The clinical-pathological characteristics of the series are summarized in the table 1. Of the risk factors analyzed, only grade 3 (p 0.001) and PR 25. No association was found between age, nodal status, tumor diameter, Ki67, Infiltrating Ductal Carcinoma vs neither Infiltrating Lobular Carcinoma nor Lympho-Vascular invasion. The cost of the genetic studies was 180000€ (1636€ each). The cost of each CT schedule (EC x 4 followed by paclitaxel x 12) was 7214€ and the total cost of 96 cases 692590€. Direct costs savings estimated from the reduction in CT treatment were 512590€ Conclusion: Our series shows that RS avoided unnecessary CT in 87% of cases and was more cost-effective than a previous series with MMP. G3 and RP 25. Table 1.Patients characteristics and clinical-pathological details from the analyzed tumorsPatient characteristicsAge, mean (range)53,76 (19 – 75)≥50y72 (65.5%) Citation Format: Ferrer M, Dorcas J, Quiroga V, Margelí M, del Barco S, Stradella A, Petit A, Falo C, Viñas G, Romeo M, Villanueva R, Cirauqui B, Vázquez S, Fernández A, Recalde S, Vethencourt A, Soler T, Pérez-Martín X, Gil-Gil M. Impact of oncotype dx genetic signature used in early breast cancer. Clinical and economic analisys of a 110 patient cohort treated in the Catalan Oncologic Institute (ICO), Spain [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-09.

Fil: Duarte Abritta, Bárbara. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Duarte Abritta, Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sánchez, Stella Maris. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Sánchez, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sánchez, Stella Maris. Universidad de Buenos Aires. Facultad de Cs. Exactas y Naturales. Departamento de Física; Argentina Fil: Abulafia, Carolina Andrea. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Abulafia, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Abulafia, Carolina Andrea. Pontificia Universidad Católica Argentina. Instituto de Investigaciones Biomédicas; Argentina Fil: Gustafson, Deborah R. State University of New York University Downstate Health Sciences University. Department of Neurology; Estados Unidos Fil: Vázquez, Silvia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Centro de imágenes moleculares; Argentina Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Departamento de Neuropatología y Biología Molecular; Argentina Fil: Castro, Mariana N. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Castro, Mariana N. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castro, Mariana N. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina Fil: Castro, Mariana N. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Servicio de Psiquiatría; Argentina Fil: Fiorentini, Leticia. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Fiorentini, Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Fiorentini, Leticia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Servicio de Psiquiatría; Argentina Fil: Villarreal, Mirta F. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Villarreal, Mirta F. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Villarreal, Mirta F. Universidad de Buenos Aires. Facultad de Cs. Exactas y Naturales. Departamento de Física; Argentina Fil: Guinjoan, Salvador M. Instituto de Neurociencias. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Guinjoan, Salvador M. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guinjoan, Salvador M. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina Fil: Guinjoan, Salvador M. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina Fil: Guinjoan, Salvador M. Universidad de Buenos Aires. Facultad de Psicología. Neurofisiología I; Argentina Fil: Guinjoan, Salvador M. Laureate Institute for Brain Research; Estados Unidos Abstract: A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aβ deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with β-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.

Objective: Increased life expectancy and exponential growth of adults suffering from Alzheimer's disease (AD) worldwide, has led to biomarkers incorporation for diagnosis in early stages. Use of neuropsychological testing remains limited. This study aimed to identify which neuropsychological tests best indicated underlying AD pathophysiology.Methods: One hundred and forty-one patients with MCI (Mild Cognitive Impairment) were studied. A neuropsychological test battery based on the Uniform Data Set (UDS) from the Alzheimer's Disease Centers program of the National Institute on Aging (NIA) was performed and amyloid markers recorded; according to presence or absence of amyloid identified by positive PIB-PET findings, or low CSF Aβ42 levels, patients were separated into MCI amyloid-(n:58) and MCI amyloid + (n = 83) cases.Results: Statistical differences were found in all memory tests between groups. Delayed recall score at thirty minutes on the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of amyloid pathology presence (AUC 0.68), followed by AVLT total learning (AUC 0.66) and AVLT Recognition (AUC 0.59) scores, providing useful cut off values in the clinical setting.Conclusions: Use of neuropsychological testing, specifically AVLT scores with cutoff values, contributed to the correct diagnosis of MCI due to AD in this SouthAmerican cohort

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p, This research was funded by the health research program of the “Instituto de Salud Carlos III” (PI14/00071) co financed with FEDER founds and for the Health Regional Management of the Junta de Castilla y León (GRS1385/A/16). J. Fernández-Mateos was partially supported by a predoctoral research grant from the Consejería de Educación—Junta de Castilla y León and the European Social Fund to CC-B (EDU/1084/2012).

Purpose To describe results of the Amyloid, Tau, Neurodegeneration (ATN) research framework classification in the Argentine‐Alzheimer's Disease Neuroimaging Initiative (arg‐ADNI) cohort. Methods Twenty‐three patients with mild cognitive impairment (MCI), 12 dementia of Alzheimer's type (DAT), and 14 normal controls were studied following the ADNI2 protocol. Patients were categorized according to presence or absence of the biomarkers for amyloid beta (Aβ; A: amyloid positron emission tomography [PET] scan or cerebrospinal fluid [CSF] Aβ42), tau (T: CSF phosphorylated‐tau), and neurodegeneration (N: CSF total‐tau, fluorodeoxyglucose [FDG]‐PET scan, or structural magnetic resonance imaging [MRI] scan). Results A+T+N+ biomarker profile was identified at baseline in 91% of mild dementia patients, 20% of early MCI patients, 46% of late MCI patients, and 14% of control subjects. Suspected non‐AD pathophysiology (SNAP, A‐T‐N+) was found in 8% of mild dementia, 20% of early MCI, 15% of late MCI, and 7% of control subjects. Conversion rates to dementia after 5‐year follow‐up were 85% in A+T+N+ MCI patients and 50% in A‐T‐N+ patients. Conclusions We present initial 5‐year follow‐up results of a regional ADNI based on AD biomarkers and the ATN classification.

Background Eribulin improves survival in pre-treated HER2-negative advanced breast cancer (ABC). However, limited data exist on co-morbidities and central nervous system (CNS) efficacy. The purpose of this study was to review eribulin’s efficacy and safety in everyday clinical practice with special focus on age, body mass index (BMI) and central nervous system (CNS) activity. Methods An observational study was conducted in a series of HER2-negative ABC patients treated from January’14-December’17 outside a clinical trial. Objective Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS), and association of clinical and pathological variables with outcome were evaluated. Results Ninety-five women were treated with at least one cycle of eribulin. Median age was 57 (33–83), and 18% were obese. Median number of prior chemotherapies for ABC was 3 (2–5) and 76% of patients had visceral metastases, including 21% with CNS involvement. Most tumors were estrogen receptor-positive (79%). ORR and stable disease (SD) at 6 months were 26.2 and 37.5%, respectively. Remarkably, relevant CNS efficacy was observed with eribulin: 20% of patients obtained partial response and 25% SD. Treatment was generally well tolerated and manageable, with 29% grade 3 and 10.9% grade 4 toxicities. Median PFS and OS were 4.1 months (CI95% 3.2–4.9) and 11.1 months (CI95% 9.5–14.7), respectively. Triple-negative disease, > 2organs involved and being younger than 70 years old were independent prognosis factors for worse OS in multivariate analysis. Most patients (75%) progressed in pre-existing metastases sites. Conclusion In everyday clinical practice, eribulin’s efficacy seems similar to pivotal trials. CNS-efficacy was observed. TNBC, > 2 organs involved and being younger than 70 years old were independent prognosis factors for worse OS. Remarkably, less incidence of grade 4-toxicity compared to previous studies was found.

Administration of chemotherapy in prostate cancer depends on patient fitness. In unfit patients, physiological impairment determines the optimum treatment. Although no consensus on assessing patient fitness currently exists, this article proposes an algorithm combining the available information for administering chemotherapy, and in particular docetaxel, in unfit patients. It was constructed by reviewing factors that can influence treatment, such as performance status, taxane-related comorbidities and nutritional status. Geriatric scales for prostate cancer patients and alternative treatment regimens for this population are also reviewed. In summary, patients require overall assessment to optimise treatment. Use of docetaxel should be restricted in unfit patients, and other options must be evaluated, because of high toxicity and low efficacy.

Background. In HER2+/HR+ breast cancer (BC), CDK4/6 inhibition combined with anti-HER2 therapy is currently being explored in phase II/III trials. However, we and others have shown that Luminal A and B subtypes (i.e. luminal disease) defined by gene expression only represent 30-50% in this group. Identification of the luminal subtype in HER2+/HR+ disease might be important since the median IC50 of palbociclib in HER2+ BC cell lines falling into the luminal subtype is lower than in non-luminal HER2+ cell lines (47.5 vs. 300 nM; Finn BCR 2011). Here, we explored, for the first time, the efficacy (progression-free survival [PFS]) of palbociclib and trastuzumab and its association with subtype in HER2+/HR+ BC. Methods. PATRICIA is an exploratory, prospective, open-label, multicenter phase II trial in advanced HER2+ BC. Patients (pts) had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of trastuzumab 6 mg/kg every 3w and palbociclib 200 mg daily for 2w and 1w off. The study was based on a Simon 2-stage design comprising 3 cohorts: ER-negative cohort A (still recruiting) and ER+ cohorts B1 and B2 (both completed). Patients in cohort B2 also received letrozole by randomization. Safety run-in phase was made for first 12 pts. For stage 1 to be successful, at least 6 pts of 15 had to be progression-free at 6 months (PFS6) in each cohort. In stage 2, up to 46 pts per cohort will be included to show a PFS6 >50%. As a secondary objective, research-based PAM50 intrinsic subtype was performed from FFPE samples using the nCounter platform. Estimates of PFS were from Kaplan-Meier curves. Univariate Cox regression analyses evaluating luminal subtype, age, performance status, treatment line, type of biopsy and endocrine treatment were evaluated. Results. Thirty-one pts with HER2+/HR+ disease were recruited in stage 1 in cohorts B1 (n=16) and B2 (n=15). Median age was 59.8y, and median number of prior lines was 3.0. The rate of PFS6 was 40.0% (6/15) and 53.3% (8/15) in cohorts B1 and B2, respectively. A total of 26 (83.9%) tumors samples (15 primary and 11 metastatic tumors) were profiled. Subtype distribution was as follows: 46.2% HER2-enriched, 23.1% Luminal B, 19.2% Luminal A and 11.5% Normal-like. Median PFS in this subgroup of patients with PAM50 data was 3.71 months. Compared to non-luminal disease, luminal disease showed a statistically significantly longer median PFS (10.37 vs. 3.53 months, p-value=0.023). The PFS hazard ratio of luminal versus non-luminal groups was 0.34 (95% CI 0.13-0.92, p-value=0.033). In addition, Luminal A signature score, as a continuous variable, was also found associated with PFS (adjusted hazard ratio=0.54, 0.31-0.92, p-value=0.023). No clinical-pathological variable was found associated with PFS. Conclusion. PAM50 subtype predicts PFS in HER2+/HR+ advanced BC treated with palbociclib and trastuzumab. Patients with non-luminal disease might not derive a large benefit from this treatment strategy concordant with the preclinical in vitro data. Our results might have important implications for current and future clinical trials evaluating CDK4/6 inhibitors in HER2+/HR+ disease. Citation Format: Ciruelos E, Villagrasa P, Paré L, Oliveira M, de la Peña L, Pernas S, Cortés J, Soberino J, Adamo B, Vazquez S, Martínez N, Perelló A, Bermejo B, Martínez E, Garau I, Melé M, Morales S, Galvan P, Pascual T, Nuciforo P, Gonzalez X, Prat A. PAM50 intrinsic subtype predicts survival outcome in HER2-positive/hormone receptor-positive metastatic breast cancer treated with palbociclib and trastuzumab: a correlative analysis of the PATRICIA (SOLTI 13-03) trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-19.

Objective The purpose of the study is to evaluate changes in body composition and nutritional status that occur throughout the oncological treatment in head and neck cancer patients. Methods A prospective cohort observational study in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) that underwent treatment with induction chemotherapy (iCT) followed by chemoradiotherapy or bioradiotherapy were invited to participate. All patients had dietetic counseling from the diagnosis and a close monitoring throughout the treatment implementing nutritional support as needed. Results From June 2011 until October 2012, 20 patients were included. Nutritional and anthropometric parameters were collected at diagnosis, post iCT, after radiotherapy, 1 and 3 months post radiotherapy. According to Patient Generated Subjective Global Assessment, 30% of patients were malnourished at diagnosis. After iCT there was an increase in weight, body mass index (BMI) and fat free mass (FFM) with almost complete improvement in dysphagia and odynophagia. Nevertheless a significant nutritional deterioration (p = 0.0022) occurred at the end of radiotherapy with 95% of patients becoming severe or moderate malnourished. Nutritional parameters such as weight, BMI and hand grip strength also decrease significantly during treatment. Conclusions Despite an intensive nutritional support from the diagnosis throughout the oncological treatment in advanced HNSCC cancer patients, nutritional status deteriorates during radiotherapy. Our findings suggest that iCT may help improve nutritional status by ameliorating the symptoms that limit the oral intake. This improvement in the nutritional status could contribute to minimize further deterioration. Further investigations are needed involving novel approaches to avoid nutritional deterioration.

Introduction: The addition of Trastuzumab(T) to chemotherapy (CT) revolutionized HER2-positive breast cancer(BC) and changed its natural history. We reviewed the efficacy of T outside clinical trials in a cancer comprehensive center. Methods: Ambiespective and descriptive study was conducted in Catalan Institute of Oncology (ICO-Barcelona). Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with LogRank test. The association of clinic-pathological variables and outcome was studied by χ2and Cox proportional hazard analysis. Results: 430 consecutive early HER2-positive BC patients (pts) were treated with adjuvant/neoadjuvant T and CT from Jan 2005 to Dec 2012. Pt basal characteristics are reported in Table 1. Neoadjuvant treatment was administrated in 230pts (54%) and in 200 (46%) in adjuvancy. Pathological complete response (pCR) in breast and nodes (ypT0/isypN0) was achieved in 48% of pts, with higher rates in hormone receptor (HR)-negative pts (62 vs 37% p=0.0005). Median duration of T: 10.6 months (m). 28%pts treated with neoadjuvant T+CT who achieved a pCR did not receive adjuvant T. Treatment discontinuation: 38pts (8.8%): 27pts due to cardiac toxicity and 4 relapsed during adjuvant T. In 87%pts, neoadjuvant CT was based on anthracyclines(A) and taxanes. Adjuvant CT: A and taxanes in 57.4%; 14%pts FAC, 15.4% A-CMF and 12% TCH. At a median follow-up of 70m (3-135), 44pts (10.4%) had relapsed: 33pts with distant M1, 9pts with only loco-regional disease and 2pts contralateral HER2-positive BC. M1 location: 46% visceral, 34% bone/lymph nodes and 20% in central nervous system (CNS). PFS was 23.4m(0-88); median OS was not reached; estimated 10 years-OS was 86.5%. Pts treated with A and taxanes had a significantly better OS compared to those treated with other CT (113 vs 98m, p= 0.009). Kaplan-Meier curve showed numerically higher relapses at 10 years in HR-positive pts (83 vs 90% p=0.8). Pts with pCR had significantly better OS (113 vs 104m, p=0.006). Pts with CNS-metastases had a significantly worse OS (13 vs 26m,p=0,02) and those with HR-negative (49 vs 24m, p= 0.033). Conclusion: In everyday clinical practice, recurrences after adjuvant/neoadjuvant trastuzumab in HER2-positive BC were less than described in the T-pivotals trials, with 10% of recurrences at a median of FU of 70m. In our series, estimated 10 years-OS was 86.5%. Pts treated with A and taxanes had a significantly better OS as well as those pts who achieved a pCR. On the contrary, pts with CNS M1 and those with HR-negative had worse prognosis. Table 1Median age51.9y (27-83)Stage I/II/III106 (25%)/ 226 (52%)/ 97 (23%)HR Positive/ Negative249 (58%)/181 (42%) Citation Format: Ortega A, Domenech M, Falo C, Gil M, Stradella A, Fernandez A, Morilla I, Villanueva R, Castany R, Vazquez S, Molina K, Bergamino M, Navarro V, Pernas S. Treatment of early HER2-positive breast cancer in trastuzumab era in everyday clinical practice: An overview after 10 years of its approval [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-32.

A pathologic complete response (pCR) in the axilla occurs in 30%-40% of patients with initially node-positive breast cancer after neo-adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node-positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy-proven node-positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki-67 > 30 (OR 1.98; 95% CI, 1.146-3.381), HER2 positivity (OR 2.6; 95% CI, 1.354-5.108), nonluminal molecular-like subtype (OR 4.15; 95% CI, 2.068-5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110-7.081). After a mean follow-up of 61 months, distant disease-free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03-8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular-like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.

Objective: To describe the Amyloid, Tau, Neurodegeneration (A/T/N) research framework classification in the Argentine-Alzheimer Neuroimaging Initiative (ADNI) cohort. Methods: 23 Mild Cognitive Impairment (MCI), 12 Alzheimer?s Disease (AD) and 14 controls were studied with the ADNI-2 protocol. Patients were categorized according to ?A? Aβ biomarkers, ?T? tau biomarker, and ?N? neurodegeneration. Results: A+/T+/N+ at baseline was found in 2/14 controls (14%), 2/10 early MCI (20%), 6/13 late MCI (46%) and 11/12 mild dementia (91%). Suspected non- AD pathophysiology (SNAP, A-/T-/N+) was found in 1/14 controls (7%), 2/10 early MCI (20%), 2/13 late MCI (15%) and 1/12 mild dementia (8%). MCI with A+/T+/N+ showed 75% (6/8) and A-/T-/N+ 50% (2/4) of conversion to dementia in two years.Conclusions: This is the first report from this region based on AD biomarkers and the new A/T/N classification. Our findings suggest that this biological classification is better for prognosis in a short time than the classical clinical one. Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad de la Costa; Colombia Fil: Pertierra, Lucia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Cohen, Gabriela. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Russo, María Julieta. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Calandri, Ismael. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Bagnati, Pablo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Tapajoz Pereira de Sampaio, Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Clarens, Florencia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Campos, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Nahas, Federico Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Vázquez, Silvia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer’s disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer’s disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases. Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer’s disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer’s-relevant brain regions even at a relatively young age. Fil: Abulafia, Carolina Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Loewenstein, David. No especifíca; Fil: Curiel-Cid, Rosie. No especifíca; Fil: Duarte Abritta, Barbara Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Sanchez, Stella Maris. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vigo, Daniel Eduardo. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Castro, Mariana Nair. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina Fil: Drucaroff, Lucas Javier. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vázquez, Silvia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Nemeroff, Charles B.. No especifíca; Fil: Guinjoan, Salvador Martín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina Fil: Villarreal, Mirta Fabiana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Background. Patients with metastatic Hormone Receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) are usually treated with CDK4/6 inhibitors combined with endocrine therapy (ET) as first line treatment. The addition of CDK4/6 inhibitors to endocrine therapy has demonstrated improved progression free survival (PFS), overall response rate (ORR) and more recently overall survival (OS). However, there is a 20% of patients who do not benefit from these drugs and those who respond eventually progress to the treatment. Notably, there is no standard treatment for patients progressing to CDK4/6 inhibitors. The information provided by the intrinsic subtypes (PAM50) highlight the potential value of BC molecular classification as a prognosis and predictive marker. Within HR+/HER2- disease, patients with non-luminal subtypes (HER2-enriched and Basal-like) present poorer prognosis than those with luminal subtypes, may be more sensitive to chemotherapy, and have higher expression of immune-related genes and tumor infiltrating lymphocytes (TILs). Recently, immunotherapy has been approved for treating metastatic triple negative breast cancer and several trials evaluating the action of immune checkpoint inhibitors are ongoing, including HR+/HER2- BC patients. TATEN study aims to evaluate the combination of pembrolizumab and chemotherapy in metastatic HR+/HER2-, PAM50 non-luminal BC. Study design. TATEN is an open-label, single arm, multicenter phase II study evaluating treatment with pembrolizumab in combination with paclitaxel in patients with locally advanced or metastatic non-luminal HR+/HER2- BC who had recurrence or progression while receiving previous therapy with a CDK4/6 inhibitor plus endocrine therapy in the adjuvant and/or metastatic setting. Tumor samples collected during advanced/metastatic disease are mandatory. No prior chemotherapy for inoperable locally advanced or metastatic BC is permitted. Eligible patients will receive pembrolizumab 200 mg every 3 weeks (on day 1 of each 21-day cycle, beginning in Cycle 1) in combination with paclitaxel 80 mg/m2 administered at days 1, 8, 15 of each 21-day cycle beginning at cycle 2. The primary endpoint of the study is to evaluate ORR according to RECIST V1.1. The study will use a Simon’s 2-stage design and will include up to 46 patients. If 6 or more responses are observed in up to 15 patients in the first stage, the trial will continue to the second stage and 31 additional patients may be evaluated for a maximum total of 46 evaluable patients. The null hypothesis will be rejected if 19 or more responses are observed. Tumor assessments will be performed every 9 weeks. Secondary endpoints include clinical benefit rate (CBR), PFS, duration of response (DoR), time to response (TtR), OS, as well as to assess the correlation of clinical benefit (ORR, PFS) with PD1 mRNA expression and early dynamic changes in ctDNA after 1 cycle of pembrolizumab (collection of blood samples at Cycle 1 Day 1, Cycle 2 Day 1 and end of treatment are mandatory). Safety and tolerability of the combination will also be assessed. Exploratory objectives include to determine ORR, PFS, DoR and TtR based on iRECIST and to identify predictive biomarkers of response to pembrolizumab plus paclitaxel. Patients will be enrolled in 7 sites in Spain. Recruitment started in July 2020. This study is financially supported by MSD. NCT04251169. Citation Format: Eva Ciruelos, Tomás Pascual, Nuria Chic, Montserrat Muñoz, Begoña Bermejo, Juan Antonio Virizuela, Mafalda Oliveira, Silvia Vázquez, Salvador Blanch, Laia Paré, Fernando Salvador, Patricia Villagrasa, Aleix Prat. Solti-1716. Targeting non-Luminal disease by PAM50 with pembrolizumab + paclitaxel in Hormone Receptor-positive/HER2-negative advanced/metastatic breast cancer patients who have progressed on or after CDK 4/6 inhibitor treatment (TATEN trial) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-04.

Purpose Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m 2 day 1; cisplatin, 75 mg/m 2 day 1; 5-fluorouracil [5-FU], 750 mg/m 2 day 1-5) and cetuximab, 250 mg/m 2 weekly (loading dose of 400 mg/m 2 ). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). Conclusions C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.

Background: Efficacy Interim results from PATRICIA phase II trial in HER2+/HR+ advanced breast cancer (BC) showed that PAM50 luminal disease was associated with larger and clinically meaningful progression-free survival (PFS) following palbociclib, trastuzumab and endocrine therapy compared to PAM50 non-luminal disease (Ciruelos E. et al, SABCS 2018). Based on these preliminary results, PATRICIA II was designed to select patients based on PAM50 and to include a randomization to a control arm. Trial Design: PATRICIA II is a randomized open-label, adaptive design, phase II study. Eligible patients must have centrally confirmed HR+/HER2+ and PAM50 Luminal A or B intrinsic subtype tumors and have received at least 1 (and no more than 4) prior lines of anti-HER2 regimens for locally advanced or metastatic BC, including a taxane and trastuzumab. Patients are randomized 1:1 to receive trastuzumab in combination with palbociclib at a standard dose of 125 mg/day orally 3 weeks on/1 week off and endocrine therapy (cohort C1) or treatment of physician’s choice (TPC): TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin, paclitaxel or docetaxel) in combination with trastuzumab (cohort C2). ET options are either an aromatase inhibitor, fulvestrant or tamoxifen. Premenopausal patients (pts) must receive ovarian suppression. Stratification factors include number of previous regimens for advanced BC (1-2 vs 3-4) and the presence of visceral disease (yes vs no). The primary objective is to assess whether the combination of palbociclib, trastuzumab and endocrine therapy is superior to TPC in terms of progression-free survival (PFS) in HER2+, PAM50 Luminal patients. The study has an 80% power with two-sided alpha=0.05 to detect a hazard ratio of 0.62 in favor of the palbociclib arm. An adaptive design will be used to compare both treatment arms. An interim analysis (IA) adjusted for multiplicity from O’Brien-Fleming method and an estimation of the conditional power (CP) will be performed at 70% of the events by an Independent Data Monitoring Committee (IDMC). Key secondary objectives are response rate, overall survival, safety, and Quality of Life. Tumor tissue and blood samples will be collected for biomarker analyses. A total of 516 patients will be screened and 232 patients will be recruited. The trial was activated in June 2019 and the recruitment is ongoing in 20 sites in Spain. The study is sponsored by SOLTI and financially supported by Pfizer. Citation Format: Eva Ciruelos, Patricia Villagrasa, Mafalda Oliveira, Sonia Pernas, Javier Cortes, Silvia Vazquez, Noelia Martínez, Antonia Perello, Begoña Bermejo, Eduardo Martínez, Isabel Garau, Mireia Melé, Alvaro Montaño, Estela Vega, Blanca Cantos, María Jose Echarri, Tomás Pascual, Jordi Canes, Pamela Céliz, Xavier González, Aleix Prat. Palbociclib in combination with trastuzumab and endocrine therapy (ET) versus treatment of physician's choice (TPC) in metastatic HER2-positive and hormone receptor-positive (HER2+/HR+) breast cancer with PAM50 luminal intrinsic subtype (SOLTI-1303 PATRICIA II): A multi-center, randomized, open-label, phase II trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-06.

The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

Fil: Pertierra, Lucia. Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia; Argentina

Summary Background Multimodal treatment for locally advanced head and neck carcinomas (LAHNC) has been reported to improve survival. However, it is less clear to what extent this survival gain is given at the expense of an impact on the quality of life of our patients. Our aim is to analyze the ongoing late toxic effects among long survivors, to determine how much these impairments affect their QoL, and if there is any factor that clearly impacts on this toxicity. Methods 152 Patients diagnosed with LAHNC were treated radically in our clinical practice, either with concomitant chemoradiotherapy or bioradiotherapy, with or without induction chemotherapy. We prospectively assessed these patients’ treatment-related late toxicities according to the Radiation Therapy Oncology Group scoring system, and patients answered a QoL question to subjectively evaluate the degree of impact caused by these sequelae in their daily life. Multivariate logistic regressions were performed to detect factors that could influence in toxicity. Results 21.9% Patients experienced grade 3–4 toxicity. Concomitant chemoradiation with cisplatin was found to be a risk factor of moderate and severe late toxicity compared to concomitant cetuximab in the adjusted analysis by RT fractionation. OR for moderate toxicity 0.292 (CI: 0.125–0.680, p = 0.004); OR for severe toxicity: 0.299 (CI: 0.0909–0.999, p = 0.05). Induction chemotherapy was found to be a protective factor for moderate late toxicity compared to concomitant treatment alone. Conclusion Patients treated with concomitant chemoradiation with cisplatin have significantly more late toxicity compared to bioradiotherapy, whereas induction chemotherapy prevents from developing moderate late toxicity.

All of these individuals had rapid onset of dementia,with cognitive fluctuation, neuropsychiatric symptoms, andseizures. The individuals underwent brain magnetic resonance imaging (MRI), CSF analysis, and tumor screening.An antibody panel performed on CSF from two of theseindividuals was positive for voltage-gated potassium channel antibodies. All had almost complete clinical recoveryafter treatment with methylprednisolone or plasmapheresis. None had any evidence of malignancy at follow-up.CSF biomarker levels were compared with those of 13individuals with a diagnosis of probable AD and 15 controls without dementia from the Argentine Alzheimer?sDisease Neuroimaging Initiative3 cohort.Ab42, t-tau, and p-tau CSF biomarkers were measuredusing commercially available enayme-linked immunosorbent assays (Innotest b- amyloid(1?42), Innotest hTAU-Agand Innotest Phosphotau(181P), respectively; Innogenetics,Ghent, Belgium).CSF t-tau levels in individuals with IME were higherthan in individuals without dementia, which strongly suggests underlying neuronal damage. P-tau was just slightlyhigher; Ab1?42 levels were low in all six cases (even lowerthan in individuals with AD) (Table 1).Case 1 underwent three lumbar punctures (at onsetand 2 and 12 months after treatment with intravenouscorticosteroids and mycophenolate mofetil). CSF biomarker levels showed higher Ab1?42 levels than in controlsand low t-tau and p-tau. These molecular findings correlated with improvement in cognitive functionCase 1 also underwent positron emission tomographywith Pittsburgh compound B (PiB-PET), which was negative for Ab1?42 deposition. Case 4 underwent brainbiopsy, which was negative for Ab immune labeling andshowed no evidence of AD neuropathology.This is the first report, to the knowledge of theauthors, on individuals with IME with a CSF biomarkerprofile mimicking that observed in individuals with AD.It has been generally accepted that low CSF Ab1?42levels indicate amyloid deposition in the central nervoussystem, but the same results were found in this group ofsix individuals with IME. The CSF biomarker levels ofCase 1 showed significant fluctuation after treatment(normalization of Ab1?42 levels and decrease in t-tauand p-tau), with a concomitant improvement in cognitivefunction. In addition, in two of the six individuals, Ab1?42 brain accumulation was excluded using a secondmethod (PiB-PET and neuropathology). These findingssuggest the possibility that APP metabolism may bealtered in individuals with IME. In this regard, APPcleavage by beta- and gamma-secretases may be alteredin a way that results in low Ab1?42 production. Also, itis possible to envision a scenario in which Ab1?42 clearance, by proteases or through the blood?brain barrier, isincreased.AD biomarkers have been assessed in previous studiesof individuals with multiple sclerosis and neuromyelitisoptica, with contradictory findings. Most studies showedno differences between controls and individuals with thedisease.4 In the case of human immunodeficiency virus?related cognitive decline, lower CSF Ab1?42 with lowertau and p-tau181 than in controls has been described.5 Asin individuals with AD, Ab1?42 was low in individualswith CNS infections, suggesting an effect of neuroinflammation on amyloid metabolism.6In conclusion, an AD-compatible CSF biomarker profile in individuals with rapid cognitive decline must becarefully interpreted to determine whether an immunemediated disorder is involved. Also, the use of AD CSFbiomarkers in individuals with cognitive disorders withacute onset is discouraged. A more-extensive evaluation ofCSF biomarkers in individuals with IME is warranted tovalidate these findings. Fil: Fernández Suárez, Marcos Nicolás. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Surace, Ezequiel Ignacio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Riudavets, Miguel Angel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Nogues, Martin. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Vazquez, Silvia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Purpose: Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods: Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results: A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P

Fil: Niikado, Matias. Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.

Background: CDK4/6 inhibition combined with anti-HER2 therapy is currently being explored in HER2-positive (HER2+) BC. Here, we report the efficacy, safety and genomic analysis of STAGE 1 of the PATRICIA phase II trial evaluating palbociclib in combination with trastuzumab (TTZ) in advanced HER2+ BC. Methods: PATRICIA is an exploratory, prospective, open-label, multicenter phase II trial. Patients (pts) had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of TTZ 6 mg/kg every 3w and palbociclib 200 mg daily for 2w and 1w off. The study was based on a Simon 2-stage design comprising 3 cohorts: estrogen receptor (ER)-negative (cohort A), ER+ (cohort B1) and ER+ with letrozole (cohort B2). Pts ER+ were randomized to cohorts B1 or B2. The trial included a safety run-in phase of the first 12 pts. For part 1 to be successful, at least 6 pts of 15 had to be progression-free at 6 months (PFS6R of 40%) in each cohort. Secondary objectives included safety and the association of the research-based PAM50 intrinsic subtyping with PFS. PAM50 was performed from FFPE samples using the nCounter platform. Multivariable Cox regression analyses evaluating PAM50 subtypes, age, performance status, treatment line, type of biopsy and endocrine treatment were performed. Results: A total of 45 pts were recruited (n=15 in each cohort). Median age was 59.5y, and median number of prior lines was 3.0. The PFS6R in cohorts A, B1 and B2 were 33.3% (5/15), 40.0% (6/15) and 53.3% (8/15), respectively. Regarding safety, grade 1-2 and 3-4 toxicities occurred in 97.7% and 84.4% of pts. The most common grade 3-4 toxicities were neutropenia (80%) and thrombocytopenia (17%). Dose reductions were required in 60% of pts. Regarding PAM50, a total of 40 (83.9%) tumors samples (22 primary and 18 metastasis) were profiled. Subtype distribution was as follows: 92.9% HER2-enriched (HER2-E) and 7.1% Basal-like in cohort A, and 46.2% HER2-E, 23.1% Luminal B, 19.2% Luminal A and 11.5% Normal-like in cohorts B1+2. No significant differences in PFS were observed across the 3 cohorts. In cohorts A+B1+B2, Luminal disease defined by PAM50 showed a higher median PFS compared to non-luminal disease (12.4 vs. 4.1 months; adjusted hazard ratio=0.37; p-value=0.052). Clinical Benefit Rate (CBR6) was 73% in Luminal Vs. 31% in non-luminals (p=0.031). In cohorts B1+B2, Luminal disease defined by PAM50 showed a higher median PFS compared to non-luminal disease (12.4 vs. 4.1 months; adjusted hazard ratio=0.30; p-value=0.025). CBR6 was 73% in Luminal Vs. 25% in non-luminals (p=0.022). No clinical-pathological variable was found associated with PFS or CBR6 in all pts or in cohorts B1+B2. Conclusion: Palbociclib in combination with TTZ is safe and active in TTZ pre-treated HER2+ advanced BC, specially within ER+ disease. Identification of the non-luminal subtypes by PAM50 might help identify pts who might not derive a large benefit from this treatment strategy regardless ER status. Our results might have important implications for current and future clinical trials evaluating CDK4/6 inhibitors in HER2+ disease. In Part 2, a total of 92 pts in cohorts B1 and B2 will be included to better assess the efficacy of this treatment strategy. Citation Format: Ciruelos E, Villagrasa P, Paré L, Oliveira M, Pernas S, Cortés J, Soberino J, Adamo B, Vazquez S, Martínez N, Perelló A, Bermejo B, Martínez E, Garau I, Melé M, Morales S, Galván P, Pascual T, Canes J, Nuciforo P, Gonzalez X, Prat A. SOLTI-1303 PATRICIA phase II trial (STAGE 1) -- Palbociclib and trastuzumab in postmenopausal patients with HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-03.

Background: Cumulative risk of stroke recurrence is about 26% at five years, with overall mortality rate of 38%. Objective: to develop a user-friendly clinical prediction algorithm of ischemic stroke recurrence to help in the design of long-term strategies for secondary prevention. Design: Historical Cohort study. Setting: Tertiary urban hospital-based practice. Patients: Subjects admitted to the hospital for a first-ever ischemic stroke. Measurements: Variables studied were clinical picture and management, previous vascular risk factors and comorbidity, Stroke subtype and severity. Predictors were determined by statistical models based on Cox regression and recursive partition analysis. The internal validity was calculated via boots trapping and its performance (predictive ability) by the statistic C. Results: 303 patients were analyzed. They were classified as having: 1) ＂high or very high＂ risk of recurrence (probability ＞ 51%) (those with left ventricular hypertrophy/hypertensive cardiomyopathy or chronic kidney disease) (21% of patients; 2) 'Intermediate' risk (probability 21-50%) (44% of patients); and 3) 'low' risk (those with age under 70 years without left ventricular hypertrophy/hypertensive cardiomyopathy nor coronary heart disease or age over 70 years, but starting therapy with anticoagulants due to an underlying embolic condition) (probability ＜21%) (35% of patients). The C statistic was 0.7557 (95% CI: 0.697-0.813) demonstrating a good predictive ability. Conclusion: A few variables organized into a clinical prediction rule, could help physician's assessment of patients with a first stroke episode admitted to a health center to improve and facilitate the decision making and course of action.

Management of residual neck disease (RND) is one of the unsolved points after bio-radiotherapy (BRT) in loco-regional advanced squamous-cell carcinoma of the head and neck (SCCHN). The aims of the study were to characterize the radiological pattern of response by computed tomography (CT) and to assess the role of positron-emission tomography (PET)/CT in this setting for a better decision-making in the indication of neck dissection (ND).We retrospectively reviewed 202 patients consecutively diagnosed with node-positive SCCHN (N1: 24; N2: 152; N3: 26) who had been treated with concomitant radiotherapy and cetuximab with or without previous induction chemotherapy between 2006 and 2013. Radiological evaluation after treatment was assessed by standard criteria using CT and in addition by PET/CT when RND was suspected in cases from 2010.There were 42 (21 %) patients who achieved complete response of the primary tumor persisting RND by CT. From this group, 24 patients were managed without PET/CT, leading to the performance of ND in 22 (92 %). On the other hand, 18 patients underwent PET/CT and ND was performed in only 6 (33 %). The overall survival was not different between both groups (p = 0.32). After histological examination and follow-up, PET/CT obtained a positive predictive value of 56 % and a negative predictive value of 89 %.Radiological response after BRT is similar to that after treatment with chemo-radiotherapy, thereby validating in this scenario the accepted CT criteria to define complete response of the neck. However, when RND is suspected by CT, PET/CT is useful to prevent unnecessary ND.

e22049Background: Colorectal cancer (CRC) is the third most common cancer worldwide. It is mostly diagnosed in elderly people, with a median age at diagnostic of 70 years. The aim of this study is ...

e22046Background: The human aging is an ongoing process, expressing a functional worsening, subjective or objective. Before to consider colorectal surgery in the elderly we have to assess the need ...

This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor–tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4–6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS). Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0–5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5–37.1), the median TTP was 9.9 months (95 % CI 6.2–12.1), and the median OS was 24.0 months (95 % CI 17.3–48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs. Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.

Two patients with mild cognitive impairment underwent C-PiB and F-FDG brain PET. Both patients had previously gone through a contrast-enhanced MRI scan that revealed extra-axial tumors next to the sphenoid wing, suggestive of meningiomas. C-PiB PET images showed a highly increased uptake by the extra-axial masses. These 2 cases represent 1.2% of our C-PiB population (n = 163). No meningioma was found with negative C-PiB uptake. The F-FDG concentration was not increased within the lesions. C-PiB could be used as a meningioma marker.

Summary: Purpose: Single photon emission computed tomography (SPECT) is widely used to evaluate functional abnormalities during the epileptic event. Changes in regional cerebral blood flow (rCBF) are well defined in patients with temporal lobe epilepsy (TLE) undergoing surgical resection. Nonetheless, the interpretation of ictal abnormalities in CBF beyond the temporal lobes has not been carefully addressed. Methods: We assessed 4 patients with pathologically proven unilateral TLE who had significant ipsilateral frontal hypoperfusion in ictal studies with no other abnormalities but chronic epilepsy accounting for such findings. Patients were assessed as candidates for surgery by interictal EEG, neuropsychological studies, brain magnetic resonance imaging, scalp electrode video-EEG monitoring, and ictal SPECT. Results: Characteristic hyperperfusion was evident over the temporal lobe ipsilateral to the EEG focus, with significant hypoperfusion over the frontal region in 3 patients. In patient 4, frontal hypoperfusion was not statistically significant. Conclusions: SPECT demonstrated relative rCBF changes beyond the epileptogenic zone in unilateral TLE. Our findings provide further insight into the pathophysiological changes underlying this condition.

Background: Congestive heart failure (HF) is a chronic, frequent and disabling condition but with a modifiable course and a large potential for improving. The aim of this project was to develop a clinical prediction model of biological and non biological factors in patients with first diagnosis of HF that facilitates the risk-stratification and decision-making process at the point of care. Methods and Results: Historical cohort analysis of 600 patients attended at three tertiary hospitals and diagnosed of a first episode of HF according Framingham criteria. There were followed 1 year. We analyzed sociodemographic, clinical and laboratory data with potential prognostic value. The modelling process concluded into a logistic regression multivariable analysis and a predictive rule: PREDICE SCORE. Age, dependency for daily basic activities, creatinine clearance, sodium levels at admission and systolic dysfunction diagnosis (HF with left ventricular ejection fraction < 40%) were the selected variables. The model showed a c-statistic of 0.763. PREDICE Score, has range of 22 points to stratifications of 1-year mortality. Conclusions: The follow-up of 600 patients hospitalized by a first episode of congestive HF, allowed us to obtain a predictive 1 year mortality model from the combination of demographic data, routine biochemistry and easy handling social and functional variables at the point of care. The variables included were non-invasive, undemanding to collect, and widely available. It allows for risk stratification and therapeutical targeting and may help in the clinical decisions process in a sustainable way. (Cardiol J 2012; 19, 6: 578-585)