ABSTRACT
Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.
Subject(s)
Biomarkers, Tumor , Immune Checkpoint Inhibitors , Lung Neoplasms , Radiosurgery , Humans , Male , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/blood , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Female , Aged , Biomarkers, Tumor/blood , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Cell-Free Nucleic Acids/blood , Prospective Studies , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Aged, 80 and over , Neoplasm Metastasis , Disease Progression , Liquid Biopsy/methods , Leukocytes, Mononuclear/metabolism , Treatment OutcomeABSTRACT
Evaluating 100 adult coronavirus disease 2019 (COVID-19) patients at a Madrid hospital, we identified a mismatch between current clinical trial designs and the evolving profile of hospitalized patients. Most patients were ineligible due to design constraints, suggesting a need to rethink trial criteria for a more accurate representation of the hospitalized COVID-19 cohort.
Subject(s)
COVID-19 , Adult , Humans , SARS-CoV-2 , Retrospective Studies , Clinical Trials as Topic , Cohort StudiesABSTRACT
PURPOSE: To identify predictors of palliation for head and neck cancer treated with the "Hypo Trial" hypofractionated radiation therapy regimen in a clinical setting. DESIGN/METHOD: We retrospectively assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30-36Gy in 5-6 biweekly fractions of 6Gy. RESULTS: The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow-up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression-free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01). CONCLUSIONS: This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.
Subject(s)
Head and Neck Neoplasms , Radiation Oncology , Head and Neck Neoplasms/radiotherapy , Humans , Palliative Care , Radiation Dose Hypofractionation , Retrospective StudiesABSTRACT
BACKGROUND AND OBJECTIVE: We examined the prognostic value of obesity and nuclear ß-catenin in patients with locally advanced rectal cancer. METHODS: We prospectively recruited a total of 98 eligible patients with locally advanced cancer for preoperative radiochemotherapy followed by total mesorectal excision. Patients' height and weight were reaorded before radiochemotherapy, and the immunohistochemical expression of nuclear ß-catenin was analyzed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier method and a Cox regression model was employed for the multivariate analysis. RESULTS: Obese patients were associated with a lower number of recurrences (3.6% vs. 34.3%, P = 0.001), and a higher DFS (95% vs. 53%; HR, 0.09; 95%CI, 0.01-0.64; P = 0.005) than non-obese patients. In the multivariate analysis, body mass index, nuclear ß-catenin expression, and the absence of lymph node metastases showed a significant increase in DFS. CONCLUSIONS: Obesity and nuclear ß-catenin are independent favorable prognostic factors for DFS in locally advanced cancer treated with preoperative radiochemotherapy. J. Surg. Oncol. 2017;115:301-306. © 2017 Wiley Periodicals, Inc.
Subject(s)
Obesity/pathology , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , beta Catenin/biosynthesis , Body Mass Index , Cell Nucleus/metabolism , Chemoradiotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Obesity/metabolism , Preoperative Care/methods , Prospective Studies , Rectal Neoplasms/metabolism , Rectal Neoplasms/surgeryABSTRACT
BACKGROUND: Preoperative chemoradiotherapy (CRT) is the cornerstone of treatment for locally advanced rectal cancer (LARC). Although high local control is achieved, overall rates of distant control remain suboptimal. Colorectal carcinogenesis is associated with critical alterations of the Wnt/ß-catenin pathway involved in proliferation and survival. The aim of this study was to assess whether CRT induces changes in the expression of ß-catenin/E-cadherin, and to determine whether these changes are associated with survival. METHODS: The Immunohistochemical expression of nuclear ß-catenin and membranous E-cadherin was prospectively analysed in tumour blocks from 98 stage II/III rectal cancer patients treated with preoperative CRT. Tumour samples were collected before and after CRT treatment. All patients were treated with pelvic RT (46-50 Gy in 2 Gy fractions) and 5-fluorouracil (5FU) intravenous infusion (225 mg/m2) or capecitabine (825 mg/m2) during RT treatment, followed by total mesorectal excision (TME). Disease-free survival (DFS) was analysed using the Kaplan-Meier method and a multivariate Cox regression model was employed for the Multivariate analysis. RESULTS: CRT induced significant changes in the expression of nuclear ß-catenin (49% of patients presented an increased expression after CRT, 17% a decreased expression and 34% no changes; p = 0.001). After a median follow-up of 25 months, patients that overexpressed nuclear ß-catenin after CRT showed poor survival compared with patients that experienced a decrease in nuclear ß-catenin expression (3-year DFS 92% vs. 43%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.02). In the multivariate analysis for DFS, increased nuclear ß-catenin expression after CRT almost reached the cut-off for significance (p = 0.06). CONCLUSIONS: In our study, preoperative CRT for LARC induced significant changes in nuclear ß-catenin expression, which had a major impact on survival. Finding a way to decrease CRT resistance would significantly improve LARC patient survival.
Subject(s)
Cadherins/metabolism , Chemoradiotherapy/methods , Colorectal Surgery/methods , Neoplasm Recurrence, Local/therapy , Preoperative Care/methods , Rectal Neoplasms/therapy , beta Catenin/metabolism , Antimetabolites, Antineoplastic/administration & dosage , Capecitabine , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prospective Studies , Rectal Neoplasms/pathology , Treatment OutcomeABSTRACT
Introducción: La hipertensión arterial frecuentemente se asocia con varios factores de riesgo cardiometabólico que pueden impactar en el éxito del tratamiento. La presencia del Síndrome Metabólico (SM) en los pacientes Hipertensos No Controlados es frecuente. El SM y la diabetes están asociados a un deficiente control de la presión arterial y a un alto riesgo cardiovascular. Objetivo: determinar la prevalencia de Síndrome Metabólico en pacientes hipertensos. Materiales y Métodos: Se analizaron 238 historias clínicas de pacientes con diagnóstico de hipertensión arterial esencial mayores de 18 años que provenían de consultorios de clínica médica de la ciudad Bahía Blanca. Resultados: Edad promedio: mujeres 67±13 años; varones 66±13 años. La prevalencia de Hipertensos No Controlados fue de 61% . En el grupo de Hipertensos No Controlados se incluyeron: 70% de los diabéticos; 78% de los obesos; 80 % de las glucemias alteradas; 80% de los HDL disminuidos en varones; 88% de los síndromes metabólicos. El 60% de los casos presentaron daño de órgano blanco. Como variable predictora de No Control de la Presión Arterial se halló el Síndrome Metabólico. Conclusiones. Los Hipertensos No Controlados presentan alta prevalencia de Síndrome Metabólico en comparación con los Hipertensos Controlados. En los Hipertensos No Controlados fueron más frecuentes: trastornos del metabolismo hidrocarbonado y lipídico, síndrome metabólico, daño de órgano blanco y consecuentemente, riesgo cardiovascular elevado. Los cambios profundos del estilo de vida juegan un rol fundamental en la reversión del síndrome metabólico.
Introduction: High blood pressure is often associated to several cardiometabolic risk factors that can affect the success of treatments. The presence of the Metabolic Syndrome (MS) in uncontrolled high blood pressure patients is quite frequent. MS and diabetes are associated to deficient control of blood pressure and cardiovascular risk. Objective: to determine the prevalence of Metabolic Syndrome in patients with high blood pressure. Materials and Methods: 238 medical records from patients with essential high blood pressure -18 years of age or older- from clinical private practices in the city of Bahía Blanca were analyzed. Results: Average age: females 67±13 years old; males 66±13 years old. The prevalence of uncontrolled high blood pressure patients was 61%. In the group of uncontrolled high blood pressure patients the following groups were included: 70% of diabetic patients; 78% of obese patients; 80% of patients with altered glycemia; 80% of males with diminished HDL; 88% of patients with metabolic syndrome. 60% of patients presented target organ damage. Metabolic Syndrome was found as predictor variable for uncontrolled blood pressure. Conclusions: Uncontrolled high blood pressure patients show high prevalence of Metabolic Syndrome compared to controlled high blood pressure patients. In uncontrolled high blood pressure patients the following conditions were more frequent: hydrocarbon and lipid metabolism disorders, metabolic syndrome, target organ damage, and consequently, high cardiovascular risk. Deep changes in life style have a major role in reversing metabolic syndrome.
Subject(s)
Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Metabolic Syndrome , Hypertension , Quality of Life , Indicators of Morbidity and MortalitySubject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/radiotherapy , Hemangiosarcoma/drug therapy , Neoplasms, Radiation-Induced/drug therapy , Paclitaxel/therapeutic use , Aged , Female , Hemangiosarcoma/etiology , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Radiation-Induced/etiology , Treatment OutcomeABSTRACT
Cuando las reservas corporales de hierro se hacen insuficientes para las necesidades de una eritropoyesis normal, hablamos de anemia ferropénica. La eritropoyesis deficiente en hierro se caracteriza por: - hipocromía y microcitosis de los eritrocitos circulantes. - concentración sérica de hierro y ferritina disminuidas. - saturación de transferrina interior al 15%. - reticulocitos disminuidos. Esta forma de anemia es la de mayor frecuencia, afecta predominantemente a la mujer (20%) y en especial durante el embarazo (50%9 y debe ser considerada un signo y no una enfermedad.
