SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment.

BACKGROUND: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. METHODS: Patients aged 18-75 years, with Eastern Cooperative Oncology Group performance status 0-2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m(-2) BID) was administered on days 1-14 every 21 days for at least two cycles. RESULTS: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1-9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). CONCLUSIONS: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules.

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

SEOM clinical guidelines for the treatment of head and neck cancer (2020)

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease (AU)

Dendritic cell uptake of iron-based magnetic nanoparticles.

We have investigated the internalization of magnetic nanoparticles (NPs) into dendritic cells (DCs) in order to assess both the final location of the particles and the viability of the cultured cells. The particles, consisting of a metallic iron core covered with carbon, showed no toxic effects on the DCs and had no effect in their viability. We found that mature DCs are able to incorporate magnetic nanoparticles in a range of size from 10 nm to ca. 200 nm, after 24 h of incubation. We describe a method to separate cells loaded with NPs, and analyze the resulting material by electron microscopy and magnetic measurements. It is found that NPs are internalized in lysosomes, providing a large magnetic signal. Our results suggest that loading DCs with properly functionalized magnetic NPs could be a promising strategy for improved vectorization in cancer diagnosis and treatment.

Prognostic value of quantitative immune alterations in melanoma patients

Introducción y objetivos: Los pacientes con cáncer presentan una alteración de la respuesta inmune.La inmunosupresión en melanoma, juega un papel importante. El objetivo de este estudio fue valorar las alteracionescueantitativas de la inmunidad en pacienets con melanoma.• Pacientes y métodos: Se obtuvieron muestras de sangre periférica en EDTA de 86 pacientes con melanoma(63 pacientes libres de enfermedad y 23 pacientes con metástasis a distancia). Los niveles de leucocitostotales, linfocitos totales, linfocitos CD3, linfocitos CD4, linfocitos CD8, linfocitos B (CD19) y linfocitosNK (CD56) fueron valorados mediante marcadores de superficie por citometría de flujo usando un CoulterEpics Elite (Coulter Corp). Los niveles de IgA, IgG, IgE e IgM fueron valorados por nefelometría usando unnefelómetro Hyland PDQ laser.• Resultados: Hubo diferencias significativas entre pacienets metastásicos y pacientes libres de enfermedaden los niveles de linfocitos totales (mediana: 2251.57 vs 1783.04/mm3, p=.001), linfocitos B (CD19)(216.1 vs 108.36/mm3, p=.010), linfocitos NK (CD56) (149.54 vs 115.2/mm3, p=.016) y niveles de IgA(241.59 vs 300.55 mg dL, p=.044) al considerarlas como variables continuas. Al considerar cada parámetro deestudio como una variable cualitativa, sólo se observaron diferencias significativas en los niveles totales delinfocitos, existiendo un 73.9% d elos pacientes con enfermedad a distancia niveles d elinfocitos por debajo de2000 células/mm3 frente a un 36.5% de pacienets libres de enfermedad (χ2 Pearson = 9.476, df = 1, p = .002).La mediana de supervivencia para 46 pacientes con niveles totales de linfocitos por encima de 2000células/mm3 fue de 965 días (DF= 65.03, IC 95% = 792.72 - 1090.30) frente a 441 días (DF= 75.61, IC 95% =292.81 - 589.19) para 40 pacientes con niveles totales de linfocitos 2000 células / mm3 (log rank = 4.54, df=1,p= .0331).• Conclusiones: Existen diferencias significativas en los niveles de algunas subpoblaciones linfocitariasy en los niveles de IgA entre pacienets metastásicos y pacienets libres de enfermedad. Los pacientes con melanomacon niveles de linfocitos totales por encima de 2000 cells/mm3 tiene una mayor supervivencia que aquelloscon niveles por debajo de 2000 cells/mm3

Purpose: The immune response is altered in patients with neoplasms. Immunosuppression hasimportant consequences in patients with melanoma. The aim of this study was to assess quantitative immunealterations in melanoma patients..• Material and methods: We obtained a peripheral blood sample in EDTA from 86 melanoma patients(63 of them disease-free and 23 with distant disease). Total leukocytes and lymphocytes, B lymphocytes(CD19), types CD3, CD4, CD8 lymphocytes, and NK lymphocytes (CD56) were counted by determining thesurface markers by flow cytometry, using a Coulter Epics Elite (Coulter Corp.). IgA, IgG, IgE and IgM wereassayed by nephelometric methods employing a Hyland PDQ laser nephelometer.• Results: We found significant differences between disease-free patients and those with active diseasewith regard to lymphocytes total count (median: 2251.57 vs. 1783.04/mm3, p=0.010), NK lymphocytes(CD56) (149.54 vs. 115.2/mm3, p=0.016), and IgA levels (241.59 vs. 300.55 mg/dl, p=0.044), when taken ascontinuous variables. When considering each parameter as a discontinuous variable, only changes in absolutelymphocyte count retained an statistical difference depending on the presence or absence of active disease,73.9% of the patients with active metastatic disease having a lymphocyte count below 2000 cells/mm3 versusonly 36.5% of the disease-free patients (c2 Pearson=9.476, df=1, p=0.002). The median survival for the 46patients with absolute lymphocyte count above 2000 cells/mm3 was 965 days (DF=65.03, IC 95%=792.72-1090.30) versus 441 days (DF=75.61, IC 95%=292.81-589.19) for the 40 patients with absolute lymphocytecount below 2000 cells/mm3 (log rank=4.54, df=1, p=0.0331).• Conclusions: There are significant differences in some lymphocyte populations and IgA levels betweenpatients with metastases and disease-free patients. Melanoma patients with absolute lymphocyte levels above2000 cells/mm3 have a longer survival than those with a lymphocyte count below 2000 cells/mm3

Abordaje terapéutico del carcinoma de pulmón no microcítico avanzado: ¿estamos “avanzando”? / Therapeutic approach of advanced non-small cell lung cancer: are we really advancing?

La quimioterapia en cáncer de pulmón no microcítico avanzado consigue un pequeño pero consistente beneficioasí como paliación de síntomas relacionados con el cáncer. En la actualidad, el tratamiento en 1ª línea sebasa en dobletes con fármacos de 3ª generación con o sin platino.Las terapias dirigidas se muestran prometedoras por su actividad y tolerancia. La aplicación de la genómicaes hoy también una vía de investigación.Actualmente, se pueden considerar segundas, terceras o más líneas de tratamiento, y también una administraciónindividualizada para performance status 2 o ancianos. Existen diferencias relacionadas con el sexo, desdesu causa a los resultados.Ciertamente, estamos avanzando en el tratamiento del cáncer de pulmón no microcítico, aunque lentamente.La investigación de fármacos más eficaces, la selección de pacientes basada en factores clínicos y la biologíadel tumor, y la óptima combinación de las diferentes modalidades terapéuticas, son la prioridad de los ensayosdel futuro

Chemotherapy has a place in the treatment of advanced non-small cell lung cancer achieving a palliation of the disease-related symptoms and a small but consistent survival benefit. At present, the first line treatment is based on third generation drugs doublets with or without platinum. Targeted therapies seem promising because of their activity and tolerance. Application of genomics to nonsmall cell lung cancer therapy represents also an interesting research way for personalized treatments. Second, third and more lines of treatment have to be considered, as well as adequate individualized treatments for performance status 2 and elderly patients. Sex-related differences have been determined in causation and results. Advances in the treatment of non-small cell lung cancer have certainly been achieved, although slowly. Investigation of more efficient drugs, selection of patients based on clinical factors and tumor biology, and the optimal way to combine the different therapeutic modalities, are to be the priority for future trials

Resultados a largo plazo del tratamiento del estesioneuroblastoma. Experiencia en Aragón (1981- / Long term results of the esthesioneuroblastoma treatment. Experience in Aragón (1981-2003)

Propósito: el estesioneuroblastoma o neuroblastoma olfatorio es un tumor infrecuente. Se han publicado sólo un millar de casos en la literatura médica. La edad media de presentación es a los 50 años, no teniendo predilección por ningún sexo. Es un tumor de agresividad local con recidivas locales tardías. Se han descrito metástasis a distancia, frecuentemente pulmón y hueso. Presentamos nuestra experiencia en el manejo y tratamiento de este tipo de tumor.- Material y métodos: entre 1981 y 2003, 8 casos de estesioneuroblastoma fueron diagnosticados en el Hospital Clínico Universitario de Zaragoza, un hospital terciario con 882 camas, que es referencia para radioterapia de alta energía en todo Aragón, por lo que con toda probabilidad, este número de casos corresponde al de diagnósticos en la Comunidad Autónoma de Aragón en ese período. Cinco varones y 3 mujeres con una mediana de edad de 60 años (rango 49-82). Los síntomas más frecuentes a la presentación incluyeron: obstrucción nasal, epistaxis, anosmia, exoftalmus, edema palpebral y tumefacción local. El estadio de Kadish al diagnóstico fue: 3 pacientes estadio B, 2 estadio C y 3 estadio D. Cirugía, radioterapia y quimioterapia fueron frecuentemente combinadas. En dos pacientes el tratamiento fue cirugía, sola en un paciente y en otro con radioterapia radical. Tres pacientes recibieron quimioterapia, sola en dos pacientes y combinada con radioterapia en el otro. Tres pacientes fueron tratados con radioterapia sólo.- Resultados: dos pacientes están vivos sin enfermedad tras 87 y 108 meses del diagnóstico y uno más está actualmente en tratamiento. Cuatro pacientes murieron con progresión a los 6, 8, 38 y 63 meses del diagnóstico. Un paciente falleció por un segundo tumor a los 36 meses del diagnóstico.- Conclusión: el control local es un requisito esencial para obtener supervivencias a largo plazo en el estesioneuroblastoma (AU)