Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: a consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

Epstein Barr virus; Prognosis; Response to treatmentVirus de Epstein Barr; Pronóstico; Respuesta al tratamientoVirus d'Epstein Barr; Pronòstic; Resposta al tractamentThe treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from AstraZeneca

Concurrent hyperfractionated radiotherapy and chemotherapy for patients with limited small-cell lung cancer. Results from a single institution

BackgroundConcurrent use of chemotherapy and twice-a-day hyperfractionated radiotherapy is an efficacious scheme to control limited disease (LD) small-cell lung cancer (SCLC).AimOur main objective was to estimate initial results in overall survival for patients with LD-SCLC treated with concomitant chemotherapy and hyperfractionated thoracic radiotherapy in routine practice. Response to treatment and toxicity were also assessed.Material and MethodsForty-nine patients with confirmed LD-SCLC were treated at the Department of Radiotherapy of the Hospital General de Catalonia (Spain) from December 1999 to February 2007. The chemotherapy regimen was cisplatin (80 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1, 2, and 3, every 21 day. The target dose to the tumor volume was 45 Gy. Prophylactic cranial irradiation (PCI), consisting of 30 Gy delivered in 15 fractions, was prescribed for all patients with a response rate >75% (23 of 30 patients).ResultsMedian follow-up was 12 months (range, 6–58 months) and median overall survival was 28.9 months. Two-year and 4-year survival rates were 56.4% and 30.1%, respectively. At 2 years, specific survival, local control, and systemic control were 64.2%, 88.8%, and 46.8%, respectively. Myelotoxicity and oesophagitis were the most severe toxicities.ConclusionsThe combined schedule – hyperfractionated irradiation plus concurrent chemotherapy – can be applied in routine practice in the context of early radiotherapy, which is considered standard treatment, with acceptable toxicity and similar results to those described in the literature

Introducción de Cetuximab en el tratamiento del carcinoma escamoso de cabeza y cuello

[spa] Esta tesis versa sobre el desarrollo clínico del anticuerpo monoclonal Cetuximab en el tratamiento del carcinoma escamoso de cabeza y cuello, en diferentes momentos de la enfermedad. En la enfermedad recurrente y metastásica, se ha realizado un estudio fase III que comparó en 1ª línea tratamiento la asociación de quimioterapia sola (esquema con Platino y 5-FU) con el mismo esquema de quimioterapia asociado a Cetuximab (esquema EXTREME). Los resultados de eficacia favoreciereon la combinación de quimioterapia con cetuximab, sin excesiva adición de toxicidad y sin repercusión en la calidad de vida evaluada por los propios pacientes. Las conclusiones han sido: 1. En comparación con el esquema de platino/fluorouracilo, la misma combinación con cetuximab mejora de forma significativa la supervivencia global en primera línea de la enfermedad recurrente/metastásica. 2. Todos los demás parámetros de eficacia (supervivencia libre de progresión, mejor respuesta global, control de la enfermedad y tiempo al fallo terapéutico) también favorecieron a la combinación con cetuximab. 3. EXTREME añade las toxicidades propias de cetuximab: cutánea, infusionales e hipomagnesisemia. Además, existe un 5% de sepsis en los pacientes con la combinación que no se dan en el grupo de QT sola. 4. La adición de cetuximab a la QT con platino/fluorouracilo no afecta de forma adversa la calidad de vida de los pacientes con enfermedad recurrente/metastásica. Además, mejoran algunos de los síntomas asociados al CECC (como el dolor o la deglución), por lo que le dan más relevancia a la combinación en una fase de la enfermedad donde el control sintomático es fundamental. 5. El número de copias del EGFR tumoral no es un biomarcador predictivo de la eficacia de la combinación de cetuximab, platino y FU en primera línea de la enfermedad recurrente/metastásica. Por tanto, el análisis de este parámetro antes del inicio de un tratamiento no aportará ninguna información relevante al clínico. Por tanto, también podemos decir que el beneficio asociado a la combinación de quimioterapia y cetuximab es independiente del número de copias del EGFR. El segundo estudio fue en enfermedad localmente avanzada, específicamente en cáncer de orofaringe y fue un estudio fase II randomizado que evaluó la eficacia y la toxicidad de la adición de 12 semanas de tratamiento adyuvante con Cetuximab semanal una vez finalizado un tratamiento concomitante con radioterapia y cetuximab. Aunque el control loco-regional al año fue un 12% superior en la rama de cetuximab adyuvante, no existieron diferencias en ningún parámetro de eficacia a partir del segundo año. Por tanto la conclusión fue, doce semanas de tratamiento adyuvante con cetuximab tras un tratamiento radical con RT + cetuximab es posible y seguro, y mejora el control de la enfermedad al final del tratamiento, y el control loco-regional al primer año. No obstante, el bloqueo en solitario del EGFR durante 12 semanas no es suficiente para eliminar la enfermedad mínima residual tras el tratamiento radical y por tanto no es capaz de mantener ese mayor control en el tiempo, con un incremento de recidivas loco-regionales en el segundo año de seguimiento, y ningún impacto sobre la supervivencia.[eng] This thesis deals on the clinical development of the monoclonal antibody Cetuximab for the treatment of squamous cell carcinoma of head and neck, at different stages of the disease. In metastatic/recurrent disease, there has been a phase III study that compared in 1st line treatment a combination of chemotherapy alone (schema with Platinum and 5-FU) with the same scheme of chemotherapy associated with Cetuximab (schema EXTREME). The conclusions have been: 1. In comparison with the Platinum/fluorouracil, the same combination with cetuximab significantly improves overall survival. 2. All other parameters of efficacy (progression free survival,best overall response, control of the disease) also favored the combination with cetuximab. 3. EXTREME toxicities of cetuximab added: skin, infusionales and hipomagnesisemia. 4. The addition of cetuximab to the chemotherapy with Platinum/fluorouracil form does not affect adversely the quality of life of patients with recurrent/metastatic disease. 5. EGFR copy number is not a predictive biomarker of the efficacy of the combination of cetuximab, Platinum and FU in recurrent/metastatic disease. The second study in locally advanced disease, specifically in oropharyngeal cancer and was a randomized phase II study that evaluated the efficacy and the toxicity of the addition of 12 weeks of adjuvant treatment with Cetuximab weekly once completed a concomitant treatment with radiotherapy and cetuximab. Although a year locoregional control was a 12% higher in the branch of adjuvant cetuximab, there were no differences in any parameter of efficiency from the second year. Therefore the conclusion was, twelve weeks of adjuvant treatment with cetuximab after radical treatment with RT + cetuximab is possible and secure, and improves the control of the disease at the end of the treatment, and first-year locoregional control. However, the blockade of EGFR during 12 weeks alone is not enough to eliminate minimal residual disease after radical treatment and therefore is not able to maintain greater control over time, with increased loco-regional recurrences in the second year of follow-up, and no impact on survival