Indicaciones del tratamiento radioterápico en el cáncer de mama

Purpose: Breast cancer is the first leading cancer-related cause of death among USA women. In Europe, breast cancer occurs as frequently as in the United States and thus we encounter this pathology on a regular basis in Oncology Services such as Radiation Oncology, General Surgery, Gynecology and Medical Oncology. Nevertheless, the number of services working with this kind of patients is increasing: Primary Health Care, Nutrition, Psycho-oncology, Rehabilitation centers, Pain Clinics and Nursing among others. Reviewing radiotherapy treatment indications shall bring this modality and its procedures closer to other medical specialties. Methods: Exposition of all clinical indications that might include radiotherapy treatment. Results: There is scientific evidence that proves that radiotherapy is needed in order to reduce locoregional risk of recurrence, which shall determine global survival. Conclusions: Breast cancer requires a multidisciplinary therapeutic approach for which radiotherapy is essential in the conservative treatment as well as in other cancer cases.Objetivo: El cáncer de mama es la primera causa de muerte por cáncer en la mujer en Estados Unidos. Esta patología es igualmente frecuente en Europa y forma parte de las con¬sultas diarias de los Servicios dedicados a la oncología (Oncología Radioterápica, Cirugía General, Ginecología, y Oncología Médica), aunque cada vez hay más Servicios implica¬dos en el manejo de estas pacientes (Atención Primaria, Nutrición, Psico-oncología, Rehabi¬litación, Unidad del Dolor, Enfermería…). La revisión de las indicaciones del tratamiento radioterápico permite acercar esta modalidad terapéutica al resto de Especialidades. Méto¬do: Exposición de todas las situaciones clínicas susceptibles de radioterapia. Resultado: Existe evidencia científica que demuestra la necesi¬dad de administrar radioterapia para disminuir el riesgo de recidiva loco-regional y ello influ¬ye en la supervivencia global. Conclusiones: El cáncer de mama precisa un abordaje tera¬péutico multidisciplinar siendo la radioterapia indispensable en el tratamiento conservador y en otros muchos casos

Indications for radiotherapy treatment of breast cancer

Purpose: Breast cancer is the first leading cancer-related cause of death among USA women. In Europe, breast cancer occurs as frequently as in the United States and thus we encounter this pathology on a regular basis in Oncology Services such as Radiation Oncology, General Surgery, Gynecology and Medical Oncology. Nevertheless, the number of services working with this kind of patients is increasing: Primary Health Care, Nutrition, Psycho-oncology, Rehabilitation centers, Pain Clinics and Nursing among others. Reviewing radiotherapy treatment indications shall bring this modality and its procedures closer to other medical specialties. Methods: Exposition of all clinical indications that might include radiotherapy treatment. Results: There is scientific evidence that proves that radiotherapy is needed in order to reduce locoregional risk of recurrence, which shall determine global survival. Conclusions: Breast cancer requires a multidisciplinary therapeutic approach for which radiotherapy is essential in the conservative treatment as well as in other cancer cases

Efficacy of a Strategy for Implementing Guidelines for the Control of Cardiovascular Risk in Primary Healthcare

Background: A number of strategies exist for the implementation of clinical practice guides (CPGs). Aim: To assess the efficacy of implementing a cardiovascular risk CPG based on an educational method involving opinion leaders, and the habitual method of dissemination among primary healthcare teams. Design and Setting: Controlled, blinded, community intervention trial randomised by clusters. Methods: 21 primary healthcare centres were randomly assigned to either the intervention arm (n = 11) or the control arm (n = 10). The study subjects were patients aged ≥45 years assigned to the centres. The overall impact of the intervention was measured as the difference between the increase in the proportion of patients whose medical records showed the recording of all the variables necessary to calculate cardiovascular risk in both arms. Analyses were performed with Generalized Lineal Model on an intention-to-treat basis. Results: 917 subjects were included at the beginning of the trial (437 in the intervention arm and 480 in the control arm). 826 subjects were included in the final evaluation (436 in the intervention group and 390 in the control arm). At the end of the trial, the recording of the variables necessary for the calculation of the cardiovascular risk in the intervention group had increased more than in the control group (difference between increases 7.49% (95% CI 4.62 - 10.35)) after adjusting for confounding variables. Conclusions: Compared to the habitual method of dissemination, the implementation of this CPG using an educational method involving opinion leaders, improved the recording of the variables needed to calculate patients’ cardiovascular risk.Funding for the trial was provided by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I). Instituto de Salud Carlos III—Fondo de Investigación Sanitaria. Expediente N˚ 031216.S

C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein

26 páginas, 6 figuras, 2 tablas.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds 63 and 65, which also potently inhibited genuine SARS-CoV-2 cell entry. Thermofluor and microscale thermophoresis studies revealed their binding to S and to its isolated receptor binding domain (RBD), interfering with the interaction with ACE2. High-resolution cryoelectron microscopy structure of S, free or bound to 2, shed light on cell entry inhibition mechanisms by these compounds. Overall, this work identifies and characterizes a new class of SARS-CoV-2 entry inhibitors with clear potential for preventing and/or fighting COVID-19.Funding for this project was provided by grants from the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global), Crue-CSIC-Santander Fondo Supera Covid-19, and CSIC grant (CSIC-COV19-082) to R.G., M.-J-P.-P., V.R., J.B., A.M., and J.-L.L. and CIBERER, Instituto de Salud Carlos III (COV20/00437) to V.R., J.B., A.M., and J.-L.L. In addition, this work was funded by grant (Covid_19-SCI) from the Generalitat Valenciana y Conselleria de Innovación, Universidades, Ciencia y Sociedad digital to R.G., and by grants PID2020-120322RB-C21 and PID2020-116880GB-I00 from the Agencia Estatal de Investigación of the Spanish Government to V.R. and J.-L.L., respectively.Peer reviewe

Quimioradioterapia neoadyuvante en cáncer de recto localmente avanzado

El tratamiento neoadyuvante con radioterapia y quimioterapia radiosensibilizante es el estándar de tratamiento para el cáncer de recto localmente avanzado (CRLA). El objetivo de este estudio es analizar la respuesta patológica tras el tratamiento neoadyuvante. Se realizó un estudio observacional descriptivo y retrospectivo en pacientes con diagnóstico de adenocarcinoma de recto desde enero 2018 a diciembre 2018 en el Servicio de Oncología Radioterápica del Hospital Universitario La Paz. Se incluyeron 51 pacientes. Un grupo de pacientes (82,4%) se trató con radioterapia tridimensional conformada (3D-CRT)con una dosis de 45 Gray (Gy) sobre pelvis y una sobreimpresión de 5,4 Gy sobre tumor primario y otro grupo (17,6%) se trató con radioterapia con técnica de arcoterapia volumétrica de intensidad modulada (VMAT) y verificación diaria con radioterapia guiada por imágenes (IGRT) con una dosis de 53,7 Gy en pelvis con sobreimpresión concurrente al tumor. La dosis de capecitabina oral fue de 850 mg/m2 dos veces al día durante el tratamiento. Todos los pacientes fueron reevaluados con resonancia magnética (RM) post-neoadyuvancia. Los pacientes se operaron entre 6-8 semanas tras quimioradioterapia. La respuesta patológica completa fue de 15,6% y la respuesta patológica parcial de 80,5% con una tasa global de downstaging de 33%. Se concluye que la quimioradioterapia neoadyuvante es un tratamiento seguro con aceptables tasas de control local en los pacientes con CRLA con escasa toxicidad aguda. Neoadjuvant treatment with radiotherapy and radiosensitizing chemotherapy is the standard of treatment for locally advanced rectal cancer (LARC). The objective of this study is to analyze the pathological response after neoadjuvant treatment. This is a descriptive and retrospective observational study in patients diagnosed with rectal adenocarcinoma from January 2018 to December 2018 at the Radiation Oncology Department of Hospital Universitario La Paz. 51 patients were included. One group of patients (82.4%) was treated with threedimensional conformal radiotherapy (3D-CRT) with a dose of 45 Gray (Gy) on the pelvis and an boost of 5.4 Gy on the primary tumor and another group (17.6%) was treated with radiotherapy with volumetric arcotherapy technique (VMAT) and daily verification with image-guided radiotherapy (IGRT) with a dose of 53.7 Gy in the pelvis with concurrent tumor boost. The oral capecitabine dose was 850 mg/m2 twice daily during treatment. All patients were reevaluated with postneoadjuvant magnetic resonance imaging (MRI). The patients underwent surgery 6-8 weeks after chemoradiotherapy. Complete pathological response was of 15.6% and partial pathological response of 80.5% with an overall downstaging rate of 33%. It is concluded that neoadjuvant chemoradiotherapy is a safe treatment with acceptable local control rates in patients with LARC with little acute toxicity.&nbsp

Adenocarcinoma de cérvix con metástasis esplénica: reporte de un caso

Los tumores sólidos hacen metástasis excepcionalmente al bazo, con una incidencia que oscila entre 2,9 a 9%. En la literatura se han descrito pocos casos de metástasis esplénicas de cáncer de cuello uterino. Se presenta el caso de paciente femenina de 59 años, con diagnóstico de adenocarcinoma de cuello uterino en estadio IVB según la estadificación de la Federación Internacional de Ginecología y Obstetricia, pobremente diferenciado, tratada con quimioterapia de inducción, seguida de radioterapia externa concomitante con cisplatino y 5 fracciones de braquiterapia endocavitaria de alta dosis, con respuesta morfológica y metabólica completa. Dos años después, la Tomografía Computarizada mostró dos lesiones sugestivas de metástasis esplénica sin encontrar enfermedad a otro nivel. Se realizó esplenectomía, confirmando la histología de adenocarcinoma cervical pobremente diferenciado con positividad a la proteína p16. Tras un año de la cirugía, la paciente está viva en remisión de la enfermedad. Las metástasis esplénicas son inusuales y, a menudo, se diagnostican de manera incidental. Por tanto, es importante un correcto seguimiento oncológico con examen físico y pruebas de imágenes. La esplenectomía es el tratamiento más adecuado.  Solid tumors exceptionally metastasize to the spleen, with an incidence ranging from 2,9 to 9%. Few cases of splenic metastases from cervical cancer have been described in the literature. Fifty-nine-year-old female patient is presented, with diagnosis of cervical adenocarcinoma in stage IVB according to the staging of the International Federation of Gynecology and Obstetrics, poorly differentiated, treated with induction chemotherapy, followed by external beam radiotherapy concomitantly with cisplatin and 5 fractions of high dose rate endocavitary brachytherapy, with a complete morphological and metabolic response. Two years later, Computed Tomography showed two lesions suggestive of splenic metastasis without finding disease at another level. Splenectomy was performed, confirming the histology of a poorly differentiated cervical adenocarcinoma with positivity for p16 protein. One year after surgery, the patient is alive in remission of the disease. Splenic metastases are rare and are often diagnosed incidentally. Therefore, a correct oncological follow-up with a physical examination and imaging tests is important. Splenectomy is the most appropriate treatment

Quimioradioterapia en cáncer de recto y tasa de respuesta patológica

Introduction. Neoadjuvant treatment with radiotherapy and radiosensitizing chemotherapy in locally advanced rectal cancer (LARC) significantly decreases local recurrence rates. Therefore the objective of this  study is to analyze the pathological complete response (PCR) and partial response (PPR) of neoadjuvant  treatment with exclusive chemoradiotherapy in patients with locally advanced rectal cancer. Matherial and Method. It has been made a study descriptive, retrospective in a cohort of patients with LARC in the January 2016 to December 2018 period in the Radiation-Oncology Department of Hospital Universitario La Paz. 140 patients were included. A group of patients (92,9%) received treatment with radiotherapy 3D conformed technique with a dose administered the 45 Gy on pelvis and a boost of 5,4 Gy on tumor and other  group (7,1%) received treatment with volumetric archotherapy radiotherapy (VMAT) guided by image (IGRT)  with a dose administered of 53,7% on pelvis with concurrent boost and. The dose of capecitabine was 850  mg/m2, twice a day during the treatment. The patients were re-evaluated with post-neoadjuvant MRI.  Patients were operated 6 to 8 weeks post chemoradiotherapy. Results. CPR was obtained of 17,1% and pPR of 80,1% with a global rate downstaging of 31,8%. Conclusion. It concludes that chemoradiotherapy neoadjuvant is a safe treatment with acceptable rates of local control in patients with LARC.  Introducción. El tratamiento neoadyuvante con radioterapia y quimioterapia radiosensibilizante en el cáncer de recto localmente avanzado (CRLA) disminuye significativamente las tasas de recurrencia local. Por tanto el objetivo de este estudio es analizar la respuesta patológica completa (RPC) y parcial (RPP) tras el tratamiento  neoadyuvante con quimioradioterapia en pacientes con CRLA. Material y método. Se realizó un estudio descriptivo, retrospectivo en pacientes con diagnóstico de CRLA  desde enero 2016 a diciembre 2018 en el Servicio de Oncología-Radioterápica del Hospital Universitario La  Paz. Se incluyeron 140 pacientes. Un grupo de pacientes (92,9%) se trató con radioterapia 3D conformada  con una dosis de 45Gy sobre pelvis y una sobreimpresión de 5,4Gy sobre tumor primario y otro grupo (7,1%)  se trató con radioterapia con técnica volumétrica y en arcoterapia (VMAT) guiado por imagen (IGRT) con una  dosis de 53,7Gy en pelvis con sobreimpresión concurrente al tumor. La dosis de capecitabina oral fue de  850mg/m2 dos veces al día durante el tratamiento. Todos los pacientes fueron reevaluados con resonancia  magnética (RM) post-neoadyuvancia. Los pacientes se operaron entre 6-8 semanas tras quimioradioterapia. Resultados. Se obtuvo una RPC de 17,1% y RPP de 80,1% con una tasa global de downstaging de 31,8%. Conclusión. Se concluye que la quimioradioterapia neoadyuvante es un tratamiento seguro con aceptables  tasas de control local en los pacientes con CRLA.

Relación entre marcadores hematológicos y la respuesta patológica completa al tratamiento neoadyuvante en cáncer de recto localmente avanzado

Introduction. Multiple haematological markers of inflammation might be related with poor prognosis in  oncological patients. Purpose. This study evaluated whether changes of haematological markers before and after chemo- radiotherapy treatment in rectal cancer might be associated to pathological complete response. Material and Methods. Medical records of 140 patients with rectal cancer who received neoadjuvant  radiotherapy followed by surgical resection were retrospectively review. Complete bloods counts (CBC) was  measured days before and after period of RT. We assessed white blood cells count (WBC), hemoglobin levels  (Hb), neutrophils count, lymphocytes count, monocytes count, neutrophil-to-lymphocye ratio (NLR), platelet- to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Results. The overall rate of pCR was 17,5%. Hematological markers had a statistically significant decrease  after CRT treatment (p<0,05), however in our analysis they do not predict complete pathological response. Conclusion. Haematological markers before and after neoadjuvant treatment do not predict tumor  responses in this study. However, a larger sample can show statistically significant results, especially in  monocytes ratio.  Introducción. Múltiples marcadores hematológicos de inflamación pueden tener relación con un peor  pronóstico en los pacientes oncológicos. Propósito. Este estudio evaluó si los cambios en marcadores hematológicos antes y después del tratamiento  quimio-radioterápico (QT-RT) en cáncer de recto pueden estar asociados con la respuesta patológica  completa. Material y método. Se revisaron retrospectivamente las historias clínicas de 140 pacientes con cáncer de  recto que recibieron tratamiento radioterápico neoadyuvante seguido de resección quirúrgica fueron  revisados retrospectivamente. Se realizó analítica completa antes y después del tratamiento QT-RT. Se  evaluaron leucocitos, hemoglobina, neutrófilos, linfocitos, monocitos, ratio neutrófilo-linfocitos (NLR), ratio  plaqueta-linfocitos (PLR) y ratio linfocitos-monocitos (LMR). Resultados. La respuesta patológica completa fue de 17,5%. Los marcadores hematológicos tuvieron una  disminución significativa tras el tratamiento de QT-RT (p<0,05), sin embargo en nuestro análisis no se  relacionó con la respuesta patológica completa, salvo el PLR (p=0,027). Conclusión. Los marcadores hematológicos antres y después del tratamiento neoadyuvante no predicen la  respuesta tumoral tras QT-RT en este estudio. Sin embargo una muestra mayor puede presentar resultados  estadísticamente signifiacativos, especialmente con los monocitos.

Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity

The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very‑low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR‑B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid‑lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle