Personalized therapy in locally advanced head and neck squamous-cell carcinoma

[ES] Introducción: El paciente con cáncer epidermoide de cabeza y cuello local/regionalmente avanzado (CECCLA) presenta características muy heterogéneas en cuanto a comorbilidades, localización y etiología tumoral . Estos factores resultan determinantes a la hora de elegir el mejor abordaje terapéutico. Material y métodos: Se ha realizado una exhaustiva revisión de la literatura para identificar los factores más determinantes a la hora de seleccionar tratamiento para estos pacientes con especial hincapié en la quimioterapia de inducción por ser la opción más discutida. Resultados: Para la selección terapéutica es necesario tomar en cuenta factores derivados del individuo siendo los más relevantes la edad y el estado general, junto a otros dependientes del tumor como estadio, localización y etiopatogenia, entre estos últimos el origen viral (HPV, EBV) cobra cada vez más importancia. Dentro de las opciones terapéuticas la quimiorradioterapia se considera el tratamiento estándar avalado por diversos ensayos clínicos y el metaanálisis. La quimioterapia de inducción ha sido una de las últimas opciones en incorporarse al inventario terapéutico, mejorando los resultados en cuento a funcionalidad y supervivencia, sin embargo la toxicidad añadida y la falta de comparaciones con la quimiorradioterapia concurrente, obligan a un uso juicioso. Conclusión: La decisión de tratamiento en el paciente con CECCLA es un proceso complejo y multifactorial que ha de realizarse necesariamente en el contexto de comités multidisciplinares que garanticen los máximos niveles de eficacia y seguridad

Induction chemotherapy in advanced laryngeal cancer.

[ES]Introducción: El cáncer de laringe es la neoplasia más frecuente de las vías aerodigestivas superiores, y de los que más impacto psicosocial producen. Material y métodos. Realizamos un estudio retrospectivo y analítico de 32 pacientes diagnosticados de carcinoma epidermoide avanzado de laringe en nuestro centro durante 48 meses consecutivos (Junio 2012-Junio 2014). Tras la revisión de las historias clínicas de forma retrospectiva, describimos el algoritmo diagnóstico-terapeútico que realizamos. Resultados: En un 9,4% de los casos se detuvo el tratamiento con preservación del órgano (TOP) por mala tolerancia. Otro 9,4% muestran respuesta completa con la quimioterapia. El 21,9 % de los pacientes precisan rescate quirúrgico. Un 9,4 % de los pacientes fallecieron por complicaciones derivadas del tratamiento. Discusión: El tratamiento del tumor laríngeo localmente avanzado es controvertido. Los pacientes que reciben TOP suponen un reto tanto terapéutico como de seguimiento y rehabilitación posteriores. Este subgrupo de pacientes supone actualmente el 65,3 % de los pacientes tratados en nuestro centro por carcinoma de laringe. Conclusiones: El TOP constituye una alternativa pero requiere individualizar cada caso. Debemos insistir en la importancia de la prevención primaria y secundaria, ante el aumento de la incidencia de la enfermedad. [EN] Introduction: Laryngeal cancer is the most common neoplasm of the upper aerodigestive tract, and more psychosocial impact produced. Material and methods. A retrospective and analytical study of 32 patients diagnosed with advanced laryngeal squamous cell carcinoma at our institution for 48 consecutive months (June 2012-June 2014). After reviewing the clinical records retrospectively, we describe the diagnostic and therapeutic algorithm we perform. Results: In 9.4% of cases treatment with organ preservation (TOP) due to poor tolerance stopped. Another 9.4% show complete response to chemotherapy. 21.9% of patients required surgical salvage. 9.4% of patients died from complications of treatment. Discussion: The treatment of locally advanced laryngeal tumor is controversial. Patients receiving TOP pose a therapeutic challenge as both tracking and Rehabilitation. This subgroup of patients currently accounts for 65.3% of patients treated in our hospital for laryngeal carcinoma. Conclusions: The TOP is an alternative but requires individualize each case. We stress the importance of primary and secondary prevention, with the increased incidence of the disease

Exemestane for breast-cancer prevention in postmenopausal women

Background: tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer. Methods: in a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured. Results: a total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P=0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P=0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P=0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths. Minimal quality-of-life differences were observed. Conclusions: exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Terapia individualizada en carcinoma epidermoide de cabeza y cuello localmente avanzado

Introduction: Locally advanced head and neck squamous cell carcinoma patients (LAHNSCC) represents a truly heterogeneous population with differences in comorbidities, primary tumor location and etiology. These are key factors in optimal treatment selection. Material and methods: An extensive literature review was made in order to identify the most relevant factor in the therapeutic decision, with special interest in induction chemotherapy as the latest and most debatable option. Results: In the therapeutic decision we have to take into account factors related to the patient, age and performance status are the most important, and others related to the tumor as stage, site of origin and etiology, between this ones l, viral subtypes (EBV and HPV) are becoming relevant in the later decades. Chemoradiotherapy is considered the gold standard treatment, supported by several randomized trials and metaanalysis. Induction chemotherapy is one of the later options appeared in the therapeutic arena, improving results in organ preservation and survival. Although a substantial increase in toxicities and lack of prospective comparisons with the standard concurrent chemoradioterapy, warrants a cautious use. Conclusions: Therapeutic choice in the LAHNSCC patient is a complex and multidimensional process, that should be carried in a specialized and multidisciplinary team that can assure the highest efficiency and security for the patientIntroducción: El paciente con cáncer epidermoide de cabeza y cuello local/regionalmente avanzado (CECCLA) presenta características muy heterogéneas en cuanto a comorbilidades, localización y etiología tumoral . Estos factores resultan determinantes a la hora de elegir el mejor abordaje terapéutico. Material y métodos: Se ha realizado una exhaustiva revisión de la literatura para identificar los factores más determinantes a la hora de seleccionar tratamiento para estos pacientes con especial hincapié en la quimioterapia de inducción por ser la opción más discutida. Resultados: Para la selección terapéutica es necesario tomar en cuenta factores derivados del individuo siendo los más relevantes la edad y el estado general, junto a otros dependientes del tumor como estadio, localización y etiopatogenia, entre estos últimos el origen viral (HPV, EBV) cobra cada vez más importancia. Dentro de las opciones terapéuticas la quimiorradioterapia se considera el tratamiento estándar avalado por diversos ensayos clínicos y el metaanálisis. La quimioterapia de inducción ha sido una de las últimas opciones en incorporarse al inventario terapéutico, mejorando los resultados en cuento a funcionalidad y supervivencia, sin embargo la toxicidad añadida y la falta de comparaciones con la quimiorradioterapia concurrente, obligan a un uso juicioso. Conclusión: La decisión de tratamiento en el paciente con CECCLA es un proceso complejo y multifactorial que ha de realizarse necesariamente en el contexto de comités multidisciplinares que garanticen los máximos niveles de eficacia y seguridad

Quimioterapia de inducción en cáncer avanzado de laringe

Laryngeal cancer is the most common neoplasm of the upper aerodigestive tract, and more psychosocial impact produced. Material and methods. A retrospective and analytical study of 32 patients diagnosed with advanced laryngeal squamous cell carcinoma at our institution for 48 consecutive months (June 2012-June 2014). After reviewing the clinical records retrospectively, we describe the diagnostic and therapeutic algorithm we perform. Results: In 9.4% of cases treatment with organ preservation (TOP) due to poor tolerance stopped. Another 9.4% show complete response to chemotherapy. 21.9% of patients required surgical salvage. 9.4% of patients died from complications of treatment. Discussion: The treatment of locally advanced laryngeal tumor is controversial. Patients receiving TOP pose a therapeutic challenge as both tracking and Rehabilitation. This subgroup of patients currently accounts for 65.3% of patients treated in our hospital for laryngeal carcinoma. Conclusions: The TOP is an alternative but requires individualize each case. We stress the importance of primary and secondary prevention, with the increased incidence of the disease.El cáncer de laringe es la neoplasia más frecuente de las vías aerodigestivas superiores, y de los que más impacto psicosocial producen. Material y métodos. Realizamos un estudio retrospectivo y analítico de 32 pacientes diagnosticados de carcinoma epidermoide avanzado de laringe en nuestro centro durante 48 meses consecutivos (Junio 2012-Junio 2014). Tras la revisión de las historias clínicas de forma retrospectiva, describimos el algoritmo diagnóstico-terapeútico que realizamos. Resultados: En un 9,4% de los casos se detuvo el tratamiento con preservación del órgano (TOP) por mala tolerancia. Otro 9,4% muestran respuesta completa con la quimioterapia. El 21,9 % de los pacientes precisan rescate quirúrgico. Un 9,4 % de los pacientes fallecieron por complicaciones derivadas del tratamiento. Discusión: El tratamiento del tumor laríngeo localmente avanzado es controvertido. Los pacientes que reciben TOP suponen un reto tanto terapéutico como de seguimiento y rehabilitación posteriores. Este subgrupo de pacientes supone actualmente el 65,3 % de los pacientes tratados en nuestro centro por carcinoma de laringe. Conclusiones: El TOP constituye una alternativa pero requiere individualizar cada caso. Debemos insistir en la importancia de la prevención primaria y secundaria, ante el aumento de la incidencia de la enfermeda

Effect of aflibercept plus FOLFIRI and potential efficacy biomarkers in patients with metastatic colorectal cancer: the POLAF trial.

Aflibercept is an antiangiogenic drug against metastatic colorectal cancer (mCRC) combined with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI); however, no antiangiogenic biomarker has yet been validated. We assessed aflibercept plus FOLFIRI, investigating the biomarker role of baseline vascular endothelial growth factor A (VEGF-A) and angiotensin-converting enzyme (ACE). Phase II trial in oxaliplatin-treated mCRC patients who received aflibercept plus FOLFIRI. The reported 135 ng/mL ACE cut-off was used and ROC analysis was performed to assess the optimal VEGF-A cut-off for progression-free survival (PFS). Overall survival (OS), time to progression (TTP), time to treatment failure (TTF), overall response rate (ORR) and disease control rate (DCR) were also assessed. In total, 101 patients were followed for a median of 12 (6-17) months. The 1941 pg/mL VEGF-A was an optimal cut-off, with a longer median PFS when VEGF-A was This study supports aflibercept plus FOLFIRI benefits, suggesting VEGF-A as a potential biomarker to predict better outcomes

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc