Lymphocyte Subsets in Defense Against New Pathogens in Patients with Cancer.

INTRODUCTION: Immunity in cancer patients is modified both by the cancer itself and by oncospecific treatments. Whether a patient's adaptive immunity is impaired depends on their levels of naive lymphocytes and other cell populations. During the COVID-19 pandemic, cancer patients are at greater risk of progressing to severe forms of the disease and have higher mortality rates than individuals without cancer, particularly while they are receiving cancer-specific therapies. An individual's protection against infection, their response to vaccines, and even the tests that determine the humoral immune response to SARS-CoV-2, depend on lymphocyte populations, meriting their study. OBJECTIVE: Estimate blood concentrations of lymphocytes involved in the immune response to new pathogens in cancer patients. METHODS: We carried out an analytical study of 218 cancer patients; 124 women and 94 men, 26-93 years of age, who were treated at the National Oncology and Radiobiology Institute in Havana, Cuba, March-June, 2020. Patients were divided into five groups: (1) those with controlled disease who were not undergoing cancer-specific treatment; (2) those undergoing debulking surgery; (3) patients undergoing chemotherapy; (4) patients undergoing radiation therapy and (5) patients currently battling infection. We evaluated the following peripheral blood lymphocyte subpopulations via flow cytometry: B lymphocytes (total, naive, transitional, memory, plasmablasts and plasma cells); T lymphocytes (total, helper, cytotoxic and their respective naive, activated, central memory and effector memory subsets); and total, secretory and cytotoxic natural killer cells and T natural killer cells. We also estimated neutrophil/lymphocyte ratios. Lymphocyte concentrations were associated with controlled disease and standard cancer therapy. For variables that did not fall within a normal distribution, ranges were set by medians and 2.5-97.5 percentiles. The two-tailed Mann-Whitney U test was used to measure the effect of sex and to compare lymphocyte populations. We calculated odds ratios to estimate lymphopenia risk. RESULTS: All cancer patients had lower values of naive helper and cytotoxic T lymphocyte populations, naive B lymphocytes, and natural killer cells than normal reference medians. Naive helper T cells were the most affected subpopulation. Memory B cells, plasmablasts, plasma cells, activated T helper cells, and cytotoxic central memory T cells were increased. Patients undergoing treatment had lower levels of naive lymphocytes than untreated patients, particularly during radiation therapy. The risk of B lymphopenia was higher in patients in treatment. The odds ratio for B lymphopenia was 8.0 in patients who underwent surgery, 12.9 in those undergoing chemotherapy, and 13.9 in patients in radiotherapy. CONCLUSIONS: Cancer and conventional cancer therapies significantly affect peripheral blood B lymphocyte levels, particularly transitional T helper lymphocytes, reducing the immune system's ability to trigger primary immune responses against new antigens.

Cardiotoxicidad por irradiación en pediatría / Cardiotoxicity by irradiation in Pediatrics

Introducción: La cardiotoxicidad depende de varios factores y se manifiesta por las alteraciones cardiovasculares inducidas por los tratamientos oncoespecíficos en la función y morfología del corazón. Objetivo: Determinar las manifestaciones de cardiotoxicidad en pacientes pediátricos. Métodos: Estudio descriptivo transversal en el que se incluyeron 79 pacientes tratados en el Instituto de Oncología y Radiobiología de Cuba con irradiación tórax-mediastino, entre enero 2008 a diciembre 2014. La enfermedad de Hodgkin estaba presente en 54 pacientes y en 25, tumores del sistema nervioso central: meduloblastomas en 19 y tumores primarios neuroectodérmicos en 6 pacientes. A todos se les hizo historia clínica con examen físico, electrocardiograma de 12 derivaciones y ecocardiograma 2D pre- y postratamientos. Se analizaron las características demográficas y clínicas. Los enfermos con Hodgkin recibieron irradiación con intensidad de 2 400 centigray y de 2 340 los pacientes con tumores del sistema nervoso central; la poliquimioterapia se realizó con antraciclinas, vincristina, vinblastina y otros. Resultados: La edad promedio de todos los pacientes fue de 7 años con predominio del sexo masculino. No se registraron síntomas o signos de cardiotoxicidad. Conclusiones: En nuestra serie de pacientes la irradiación del área cardiaca aparentemente es bien tolerada, sin aparición temprana de cardiotoxicidad, ni en periodos de seguimiento de hasta 9 años. Aparecieron naúseas y leucopenias transitorias en algunos casos. No existió diferencias en las toxicidades en los grupos de tumores estudiados Es necesario mantener un seguimiento estrecho para descartar la aparición de cardiotoxicidad en años siguientes(AU)

Introduction: Cardiotoxicity depends on various factors and it is evident in cardiovascular alterations induced by oncologic treatments directed to the heart´s function and morphology. Objective: To determine the symptoms of cardiotoxicity in pediatric patients. Methods: Descriptive and cross-sectional study in which there were included 79 patients treated in the Cuban Institute of Oncology and Radiobiology with thorax-mediastine irradiation from January 2008 to December 2014. Hodgkin disease was present in 54 patients, tumors of the central nervous system in 25, medulloblastomas in 19, and neuroectodermic primary tumors in 6. All the patients underwent physical examination, 12 -lead electrocardiogram and pre- and post-treatment 2D echocardiograms to include in the clinical records. The demographic and clinic characteristics were analyzed. Hodgkin disease's patients received irradiation with 2 400 cGy intensity and the patients presenting tumors in the central nervous system with 2 340 cGy. Polychemotherapy was carried out with antracyclines, vincristine, vinblastine and others. Results: Average age of all patients was 7 years with predominance of male sex. Symptoms of cardiotoxicity were not recorded. Conclusions: In the serie of analyzed patients, irradiation in the heart area was apparently well beared by the patients, without early appearance of cardiotoxicity, not even in follow up periods of 9 years. Transitory nausea and leucopenia appeared in some cases. There are no differences in the toxicities of the different tumour's groups studied. It is necessary to keep the regular follow up to rule out the appearence of cardiotoxicity in the next years(AU)

Transición a Radioterapia Tridimensional con escalada de dosis: Impacto en los Gliomas de alto grado / Transition to three-dimensional radiotherapy with dose scale: Impact on high-grade Gliomas

Introducción: La radioterapia externa con dosis altas, ha incrementado el efecto terapéutico en Gliomas Anaplásicos. El propósito de nuestro estudio fue demostrar la eficacia de la radioterapia conformada tridimensional con altas dosis en estos pacientes. Métodos: Estudio retrospectivo-prospectivo y descriptivo realizado en 45 pacientes adultos con diagnóstico de Glioma de alto grado supratentorial, índice de Karnofsky ≥ 70, sin previa quimioterapia o inmunoterapia; con exéresis quirúrgica y radioterapia postoperatoria estándar bidimensional óconformada tridimensional en el Instituto de Oncología de Cuba del 2004-2007. Se excluyeron los casos no operados. Se utilizó Kaplan Meier y regresión de Cox entre las variables. Resultados: La edad promedio fue 55 años, relación sexo hombre/mujer fue 27/18 y el Glioblastoma resultóla histología más frecuente. Predominóla exéresis subtotal del tumor y radioterapia postoperatoria con dosis entre 60-70 Gy. La supervivencia fue mayor en pacientes con mejor pronóstico, resección tumoral total y radioterapia con altas dosis. La supervivencia global fue de 13 meses y la media (Kaplan-Meier) fue significativamente mejor en los pacientes con dosis altas de radioterapia tridimensional (16 vs 9 meses) P<0.001. La supervivencia a 1 y 2 años, fue del 51 % y 28 % respectivamente en el grupo de altas dosis, asícomo del 28% y 16% respectivamente en el grupo de dosis estándar, sin evidenciarse un incremento en las toxicidades. Conclusiones: La intensificación de la radioterapia local con escalada de dosis es recomendable para los pacientes con Gliomas de alto grado y factores pronósticos favorables

Introduction: High-dose with external beam radiotherapy has been shown to enhance the radiation effect in anaplastic gliomas. The aim of this trial is to report on the efficacy of 3D conformal radiotherapy (3D-CRT) for patients with intracranial malignant gliomas. Methods: A retrospective-prospective and descriptive study was made from 45 patients with supratentorial high-grade gliomas,Karnofsky performance scale ≥ 70, no previous chemotherapy/ immunotherapy treatment, who received postoperative 2D standard or 3D-CRTat the Oncology Institute of Cuba from 2004-2007. Results: The median age of patients was 55 years, gender (M/F:27/18). Glioblastoma histology, subtotal resection, and postoperative radiotherapy (60-70Gy) were the most frequently. The survival time was much better in patients who were better prognosis, gross total resection and high-dose 3D-CRT postoperatively .The overall survival was 13 months and the estimated median survival (Kaplan-Meier) was better in high-dose group (16 vs 9 months), and the 1 and 2 yearssurvival rates were 51% & 28%, respectively for 3D-CRT group; and 28% & 16% for 2D-RT. No significant treatment toxicities were observed. Conclusions: Intensification of local radiotherapy with dose escalation is feasible for patients with high-grade gliomas and good prognostic factors.

Complicaciones agudas de la radioterapia externa convencional en el paciente con cáncer de próstata / Acute complications of conventional external radiotherapy treatment in patients with prostate cancer

Se realizó un estudio descriptivo y retrospectivo con la finalidad de identificar las toxicidades agudas más frecuentes, provocadas por el tratamiento de radioterapia externa convencional en dos dimensiones, en los pacientes diagnosticados con cáncer de próstata en el Instituto Nacional de Oncología y Radiobiología (INOR), en el período comprendido entre 2008 y 2012. Además se evaluaron otras variables de interés para una mejor descripción de la serie. El universo lo constituyeron los adultos con cáncer de próstata inscritos en el INOR (235) y la muestra fue de 138 individuos con cáncer de próstata confirmado y con criterio de recibir tratamiento radiante. Se obtuvo la información a través de la revisión de las historias clínicas que se encontraban en el archivo del Departamento, previa confección de un cuestionario, que se utilizó como instrumento para la recolección de los datos y que permitió evaluar las variables trazadas. Los resultados obtenidos fueron expresados en porcientos y se plasmaron en tablas. Se pudo llegar a la conclusión de que predominaron las edades comprendidas entre 60 y 79 años, los pacientes en etapa clínica III, así como la enfermedad de alto riesgo. Las toxicidades que prevalecieron fueron la disuria, la diarrea y la polaquiuria (AU)

A descriptive and retrospective study was carried out with the objective to describe the main acute toxicities of the patients with prostate adenocarcinoma who received 2 dimensional external beam radiotherapy treatments at the National Institute of Oncology in Havana City, from 2008 to 2012. Others variables were examined to get a better description of the study. The universe was made up by all the patients diagnosed with prostate cancer and admitted at the National Institute of Oncology in Havana City (235 patients) and the sample was formed by 138 adults with confirmed prostate adenocarcinoma who were applied a questionnaire to collect the data that permitted to assess the variables established. The results obtained were expressed in percentage and were represented in charts. The conclusions allowed knowing that the ages between 60-79 years old and the clinical stage III prevailed as well as the high risk disease. The mos t common acute toxicities were: dysuria, diarrhea and miccional urgency (AU)

Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck.

The prognosis of patients with advanced head and neck cancer remain dismal. For this tumor type, elevated levels of EGFR are associated with a shorter disease free survival and time to treatment failure, reflecting a more aggressive phenotype. Nimotuzumab is a humanized monoclonal antibody that recognizes domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by cetuximab and the binding site for EGF. In order to assess the efficacy of nimotuzumab in combination with radiotherapy, a controlled, double blind, randomized clinical trial was conducted in 106 advanced squamous cell carcinoma of the head and neck patients, mostly, unfit for chemoradiotherapy. Control patients received a placebo and radiotherapy. Treatment was safe and the most frequent adverse events consisted on grade I or II asthenia, fever, headache and chills. No skin rash was detected. A significant complete response rate improvement was found in the group of patients treated with nimotuzumab as compared to the placebo. In the intent to treat analysis, a trend towards survival benefit for nimotuzumab treated subjects was found. The survival benefit became significant when applying the Harrington-Fleming test, a weighted log-rank that underscores the detection of differences deferred on time. In addition, a preliminary biomarker investigation showed a significant survival improvement for nimotuzumab treated patients as compared to controls for subjects with EGFR positive tumors. All patients showed a quality of life improvement and a reduction of the general and specific symptoms of the disease.