Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Analysis of the association of HER-2 low carcinomas and PAM50 assay in hormone receptor positive early-stage breast cancer.

BACKGROUND: HER2-low has emerged as a new predictive biomarker in metastatic breast cancer. However, its prognostic value in early-stage carcinomas needs to be revisited. We aimed to evaluate the association of HER2-low carcinomas with PAM50 risk groups combined with clinicopathological variables in early breast cancer. METHODS: We conducted a retrospective analysis of 332 patients with early-stage breast cancer that underwent PAM50 signature analysis between 2015 and 2021at Hospital Universitario 12 de Octubre (Madrid, Spain). Clinical and pathological variables were collected from medical records. After adjusting for potential confounders, we estimated Odds Ratio (OR) and 95% confidence interval for high-risk PAM50 subgroup, comparing HER2-low versus HER2-zero carcinomas by multivariable logistic regression. P values below 0.05 were deemed statistically significant. RESULTS: 192 (57%) patients were classified as HER2-low carcinomas. Median follow-up was 34 months. Adjusted OR for high-risk PAM50 when comparing HER2-low versus HER2-zero carcinomas was 1.31 (95% CI: 0.75-2.30, p = 0.33). The multivariable model detected significant associations for Ki-67% (≥20% vs. <20%: OR = 4.03, 95% CI: 2.15-7.56, p < 0.001), T staging category (T2/T3 vs. T1: OR = 3.44, 95% CI: 1.96-6.04, p < 0.001), progesterone receptor (PR ≥ 20% vs. <20%: OR = 0.44, 95% CI: 0.23-0.83, p = 0.01), nodal staging category (N+ vs. N0: OR = 3.8, 95% CI: 1.89-7.62, p < 0.001) and histological grade (grade 2 vs. 1: OR = 2.41, 95% CI: 1.01-5.73, p = 0.04; grade 3 vs 1: OR = 5.40, 95%CI: 1.98-14.60, p = 0.001). CONCLUSIONS: In this early-stage breast cancer cohort, HER2-low was not associated with a high-risk PAM50 compared to HER2-zero carcinomas. Ki-67 ≥ 20%, T2/T3, histological grade 2/3, N+ and PR<20% were significantly associated to a high-risk PAM50.

Proteína C reactiva como biomarcador predictivo de fuga anastomótica en cirugía oncológica colorrectal: estudio de cohorte retrospectivo / C-reactive protein as a predictive biomarker of anastomotic leak in colorectal cancer surgery: A retrospective cohort study

Introducción. La fuga anastomótica es la complicación más grave del tratamiento quirúrgico del cáncer de colon por su alta morbimortalidad. El diagnóstico evidente, manifestado por la salida de contenido intestinal por drenajes o la herida quirúrgica, ocurre tardíamente (entre el 6º y 8º día). El objetivo de este trabajo fue estudiar la variación de los valores de la proteína C reactiva postoperatoria para hacer un diagnóstico precoz. Métodos. Estudio observacional, analítico, retrospectivo, de una cohorte de pacientes con neoplasia, en quienes se realizó cirugía oncológica con anastomosis intestinal, entre enero de 2019 y diciembre de 2021. Se midieron los valores en sangre de proteína C reactiva postoperatoria (1°, 3° y 5° días). Resultados. Se compararon 225 casos operados que no presentaron fuga con 45 casos con fuga. En los casos sin fuga, el valor de proteína C reactiva al 3º día fue de 148 mg/l y al 5º día de 71 mg/l, mientras en los casos con fuga, los valores fueron de 228,24 mg/l y 228,04 mg/l, respectivamente (p<0,05). Para un valor de 197 mg/l al 3º día la sensibilidad fue de 77 % y para un valor de 120 mg/l al 5º día la sensibilidad fue de 84 %. Conclusión. El mejor resultado de proteína C reactiva postoperatoria para detectar precozmente la fuga anastomótica se observó al 5º día. El valor de 127 mg/l tuvo la mejor sensibilidad, especificidad y valor predictivo negativo, lo cual permitiría el diagnóstico temprano y manejo oportuno de esta complicación

Introduction. Anastomotic leak is the most serious complication of surgical treatment of colon cancer due to its high morbidity and mortality. The obvious diagnosis manifested by the exit of intestinal content through drains or the operative wound, occurs late (between the 6th and 8th day). The objective of this work was to study the postoperative C-reactive protein values to make an early diagnosis. Methods. Observational, analytical, retrospective study of a cohort of patients undergoing colorectal surgery for neoplasia, between January 2019 and December 2021, who underwent oncological surgery with intestinal anastomosis and measured CRP blood values on 1st, 3rd and 5th post-operative days. Results. Two-hundred-twenty-five operated cases that did not present leaks were compared with 45 cases with leaks, with CRP values on the 3rd and 5th day of 148mg/l and 71mg/l in cases without leakage and CRP values of 228.24mg/l and 228.04 mg/l in cases with leakage on the 3rd and 5th day, respectively (p<0.05), CRP value of 197mg/l on the 3rd day has a sensitivity of 77%; CRP value of 120mg/l on the 5th day, has a sensitivity of 84%. Conclusions. The best result for CPR to early diagnosis of anastomotic leak was observed on the 5th day, having the value of 127 mg/l the best sensitivity, specificity and NPV, which would allow early diagnosis and timely management

Cambios en la densidad de recursos humanos en salud durante la epidemia de COVID-19 en el Perú, abril - agosto 2020

Objetivo. Analizar los cambios en la Densidad de Recursos Humanos en Salud (DRHS) en el Ministerio de Salud a nivel regional y provincial en el Perú; a fin de describir la respuesta del sistema de salud sobre este componente durante la epidemia de COVID-19. Métodos. Estudio descriptivo basado en el análisis de la base de datos nacional de INFORHUS del Ministerio de Salud. Para el cálculo de la DRHS, se consideró como numerador al personal de salud registrado en la base de INFORHUS y como denominador a la población adscrita al Seguro Integral de Salud - SIS. Se excluyó a personal de salud que falleció y aún estaba registrado, y a personal diagnosticado de COVID-19 por prueba rápida o molecular durante los meses considerados en el análisis. Se analizaron los cambios porcentuales de DRHS entre los meses de abril hasta agosto de 2020 a nivel regional y provincial en el Perú. Resultados. En el periodo abril-agosto la DRHS a nivel nacional se incrementó en un 5,1%. A nivel regional este incremento se logró en 15 de las 25 regiones con una variación desde 0,2% hasta 12,3%, y se visualizó una reducción brusca y sostenida del personal nombrado, juntamente con un incremento del personal con contratos temporales. En el resto de las regiones se visualizó una reducción de DRHS la cual varió entre -0,7% hasta -7,7%. Conclusiones. La DRHS en el Perú mostró un leve incremento a nivel nacional durante el primer periodo de cuarentena por la pandemia de COVID-19; sin embargo, este resultado no ha sido equitativo en las diferentes regiones y provincias a nivel nacional. Esto sugiere una limitación en el alcance de las medidas tomadas por el gobierno, y la necesidad de tomar acciones para el fortalecimiento de la situación de salud y despliegue de RHUS en los sectores más desfavorecidos.

Objective. To analyze the changes in the density of human resources in health (DHRH), in the Ministry of Health at the regional and provincial level in Peru, in order to describe the response of the health system on this component during the COVID-19 epidemic. Methods. Descriptive study based on the analysis of the INFORHUS national database of the Ministry of Health. To calculate the DHRH, the health personnel registered in the INFORHUS database were considered as the numerator and the population assigned to the Seguro Integral de Salud - SIS as the denominator. Health personnel who died and were still registered, and personnel diagnosed with COVID-19 by rapid or molecular testing during the months considered in the analysis, were excluded. The percentage changes of DHRH between the months of april to august 2020 were analyzed at the regional and provincial level in Peru. Results. In the april-august 2020 period, in response to the first phase of the COVID-19 pandemic, Peru increased the DHRH by 5,1%. At the regional level, this increase was achieved in 15 of the 25 regions with a variation from 0,2% to 12,3%, and a sharp and sustained reduction in appointed personnel was observed, together with an increase in personnel with temporary contracts. In the rest of the regions, a reduction in DHRH was observed, which ranged from -0,7% to -7,7%. Conclusions. DHRH in Peru showed a slight increase at the national level during the first quarantine period due to the COVID-19 pandemic, however, this result has not been equitable in the different regions and provinces at the national level. This suggests a limitation in the scope of the measures taken by the government, and the need to take actions to strengthen the health situation and deployment of human resources in health in the most disadvantaged sectors.

Outcomes of COVID-19 in Patients With Lung Cancer Treated in a Tertiary Hospital in Madrid.

Background: Cancer patients represent a vulnerable population for COVID-19 illness. We aimed to analyze outcomes of lung cancer patients affected by COVID-19 in a tertiary hospital of a high-incidence region during the pandemic. Methods: We annotated 23 lung cancer patients consecutively diagnosed with COVID-19 at our institution (HGUGM; Madrid, Spain) between March 4th, 2020 and May 12th, 2020. Only patients with a confirmatory SARS-CoV-2 RT-PCR were included in the study. Results: All patients had at least 1 COVID-19 related symptom; cough (48%), shortness of breath (48%), fever (39%), and low-grade fever (30%) were the most common. Time from symptoms onset to first positive SARS-CoV-2 PCR was 5.5 days (range 1-17), with 13% of cases needed from a 2nd PCR to confirm diagnosis. There was a high variability on thoracic imaging findings, with multilobar pneumonia as the most commonly found pattern (74%). Main lab test abnormalities were low lymphocytes count (87%), high neutrophil to lymphocyte ratio -NLR- (78%), and elevated inflammatory markers: fibrinogen (91%), c-reactive protein -CRP- (87%), and D-dimer (70%). In our series, hospitalization rate was 74%, 39% of patients developed acute respiratory distress syndrome (ARDS), and the case-fatality rate was 35% (8/23). 87% of patients received anti-viral treatment (87% hydroxychloroquine, 74% lopinavir/ritonavir, 13% azithromycin), 43% corticosteroids, 26% interferon-ß, 4% tocilizumab, and 82% of hospitalized patients received anticoagulation. High-oxygen requirements were needed in 39% of patients, but only 1 pt was admitted for invasive MV and was discharged 42 days after admission. Multiple variables related to tumor status, clinical baseline conditions, and inflammation markers were associated with mortality but did not remain statistically significant in a multivariate model. In patients with lung cancer receiving systemic therapy (n = 242) incidence and mortality from COVID-19 were 4.5, and 2.1%, respectively, with no differences found by type of treatment. Conclusions: Lung cancer patients represent a vulnerable population for COVID-19, according to the high rate of hospitalization, onset of ARDS, and high mortality rate. Although larger series are needed, no differences in mortality were found by type of cancer treatment. Measures to minimize the risk of SARS-CoV-2 infection remain key to protect lung cancer patients.

Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations.

The poly-(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib, have recently been approved for use in patients with metastatic breast cancer (BC) and germline BRCA 1 or 2 mutations due to improved progression-free survival compared to chemotherapy. An increasing number of clinical trials are evaluating the role of PARP inhibitors (PARPi) in BC, alone and in combination with other therapies (including immunotherapy), as well as in earlier stages of the disease. This review describes the unique mechanism of action of these drugs and puts into clinical context the results of pivotal clinical trials. We also discuss the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling.

Green microalga Scenedesmus acutus grown on municipal wastewater to couple nutrient removal with lipid accumulation for biodiesel production.

The green microalga Scenedesmus acutus was cultivated in two different municipal wastewater discharges (pre- and post-treated), and was compared to a culture medium with basic nutrients (20% of N, P, K), in order to study the simultaneous potential of nutrient removal and lipid accumulation ability. The highest level of nutrient removal was found in the pretreated wastewater discharge (achieving a high removal of phosphorus [66%] and organic nitrogen [94%]). Likewise, better results on biomass productivity and lipid accumulation were found in cultures using pretreated wastewater compared to enriched medium, obtaining 79.9 mg/L, and 280 mg/L, respectively. Since the best results were found in pretreated wastewater, the biodiesel preparation was performed using said medium at small-scale. After cultivation, 249.4 mg/L of biodiesel were obtained. According to this analysis, S. acutus could be used for wastewater treatment producing biomass with a suitable content of lipids, convenient for biodiesel production.