RESUMO
PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].
RESUMO
OBJECTIVE: Larynx preservation is the current standard for locally advanced (LA) laryngeal/hypopharyngeal tumors, but not all patients respond as expected. TALK score model measures four variables (T-staging, albumin levels, liquor consumption and Karnofsky score) to determine which cases are best suited to preservation treatment scheme. We aimed to validate this prognostic model in a Southern European population. METHODS: We retrospectively evaluated 175 patients diagnosed from July 2008 to December 2015 with LA laryngeal/hypopharyngeal carcinoma and treated with a laryngeal preservation scheme comprising induction chemotherapy followed by concomitant chemotherapy and radiotherapy. We applied the TALK score model to predict larynx preservation rate. RESULTS: Of the 175 patients evaluated, 96.6% were men, 98.3% were smokers and 77.1% misused alcohol. Tumors were laryngeal 66.3% vs 33.7% in hypopharynx, and all were either stage III (37.7%) or stage IV (62.3%). TALK prognostic subgroups were: good risk 40.0%; intermediate risk 52.5%; and poor risk 7.5%. With a median follow-up of 40.1 months, larynx preservation rate, laryngectomy-free survival and overall survival at 3 years was 84.5%, 63.7% and 68.2%, respectively. Although TALK score was not predictive of 3-year larynx preservation rate (good risk 85.5%; intermediate risk 83.1%; poor risk 91.6%), it was predictive of 3-year overall survival (good risk 81.9%; intermediate risk 62.9%; poor risk 33.5%) and 3-year laryngectomy-free survival (good risk 75.6%; intermediate risk 59.6%; poor risk 30.7%). CONCLUSION: TALK model could predict OS and laryngectomy-free survival, helping clinicians to decide which patients should avoid laryngeal preservation and undergo laryngectomy after diagnosis.
Assuntos
Neoplasias Laríngeas , Laringe , Masculino , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Laringe/cirurgia , Laringe/patologia , Neoplasias Laríngeas/patologia , Resultado do Tratamento , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: The Catalan Institute of Oncology (ICO) is a Comprehensive Cancer Center (CCC) responsible for the oncological care of 46% of the Catalan population. OBJECTIVE: Given the increasing and ongoing approval of onco-hematological treatments, the professionals at the ICO decided to have clinical practice guidelines (called ICOPraxis) based on available evidence. In this report, we intend to share how the ICOPraxis has developed and what its impact has been in the 14 years it has been running. RESULTS: In the 14 years, since the project has been running, 17 clinical practice guidelines (some of them with several editions) have been prepared for major onco-hematology clinical conditions. These guidelines will be utilized in the four ICO centers (Girona, Badalona, Tarragona, and Hospitalet) and ICO works in a network with 18 regional hospitals. Between 2018 and 2022, the guidelines have been viewed 38.645 times and downloaded 24.614 times, with an average time spent on each page of 3 min. The ICOPraxis have been consulted in 25 countries in America (3.163 views), 20 countries in Europe (35.365 views), 10 countries in Asia (36 views), and 3 countries in Africa (12 views). The country with the highest number of downloads is Spain with a total of 34.742 downloads (Analytics [Internet]). CONCLUSION: The ICOPraxis have succeeded in establishing an evidence-based system that facilitates prescription decision-making according to the established harmonization process and reduction in variability in treatments, increasing equity in our population.
Assuntos
Doenças Hematológicas , Hematologia , Humanos , Europa (Continente) , Espanha , OncologiaRESUMO
Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy (RT) is the cornerstone of locoregional treatment of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.
Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologiaRESUMO
Cisplatin is the standard of treatment for squamous cell carcinoma of the head and neck (SCCHN) that has demonstrated efficacy, either in locally advanced disease when combined with radiotherapy at high doses, or in metastatic/recurrent disease when combined with other agents. However, the usual toxicities related to cisplatin, such as neurotoxicity, nephrotoxicity, ototoxicity, and hematologic toxicities, especially when high doses have been administered, have important implications in the patients' quality of life. The decision to administer cisplatin depends on several patient factors, such as age, performance status, weight loss, comorbidities, previous toxicities, chronic viral infection, or even the current SARS-CoV-2 pandemic. In order to establish recommendations for the management of patients with SCCHN, a group of experts in medical and radiation oncology from Spain and Latin-American discussed how to identify patients who are not candidates for cisplatin to offer them the most suitable therapeutic alternative.
RESUMO
The clinical and biological heterogeneity of head and neck cancer (HNC) is paralleled by a plethora of different symptoms that affect the patient's quality of life. These symptoms include, for instance, pain, fatigue, nutritional issues, airways obstruction, voice alterations and psychological distress. In addition, patients with HNC are prone to a high risk of infection, and may also suffer from acute complications, such as hypercalcemia, spine compression by bone metastasis or bleeding. Prolonging survival is also an inherent expectation for all patients. Addressing the above needs is crucial in all patients with HNC, and especially in those with recurrent and/or metastatic (RM) disease. However, research on how to address patients' needs in RM-HNC remains scarce. This paper defines patients' needs for RM HNC and presents an Expert Opinion on how to address them, proposing also some lines of research.
Assuntos
Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Prova Pericial , Fadiga , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Recidiva Local de NeoplasiaRESUMO
INTRODUCTION: Radiation resistance is a major cause of death in cancer patients. Cancer cells react during radiotherapy by re-programming specific cell functions that may confer resistance to radiation. The understanding of this complex process is hindered due to the lack of appropriate study models. We describe an experimental development of a radioresistant isogenic cancer cell line, and its molecular characterization. MATERIALS AND METHODS: A431-cultured cells were irradiated for 7 month until 85 Gy. Then, a selected single cell was left to grow as stable A431-R cell line. Clonogenic assay was used to determine cell survival, the α and ß parameters of the LQ model, and the mean inactivation dose. The DNA repair ability of cells was evaluated by pulsed-field electrophoresis method. Differential effect of fractionated radiation was ultimately tested in xenografts. Furthermore, we used a wound healing assay, Western blot for EGFR, AKT and ERK1/2 and ELISA test for vascular endothelial growth factor (VEGF) secretion. Finally we explored CD44 marker and cell cycle distribution. RESULTS: The established A431-R cell line showed radiation resistance in clonogenic assays, repair of radiation-induced DNA fragmentation and xenografted tumours. The radiation resistance was associated with in vitro higher cell growth and migration, increased levels of former oncoproteins, and secretion of VEGF. CONCLUSIONS: In this model, the emergence of radiation resistance was associated with the acquisition of biological traits that support more aggressive behaviour of cancer cells. We have generated a model that will be useful for mechanistic studies and development of rational treatments against radiation resistance in cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Tolerância a Radiação , Animais , Apoptose , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Ciclo Celular , Movimento Celular , Proliferação de Células , Relação Dose-Resposta à Radiação , Feminino , Citometria de Fluxo , Raios gama , Humanos , Receptores de Hialuronatos/metabolismo , Camundongos , Camundongos Nus , Fenótipo , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer. OBJECTIVE: The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS). MATERIALS AND METHODS: Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m(2) plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m(2) if MTD was not reached. RESULTS: MTD of docetaxel was 20 mg/m(2). Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m(2). Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0-22.3) and the median OS was 15.1 months (95%CI: 0-35.9). Grade 3-4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia). CONCLUSIONS: Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Taxoides/uso terapêutico , Adulto , Idoso , Terapia Combinada/efeitos adversos , Docetaxel , Fracionamento da Dose de Radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia/efeitos adversosRESUMO
Antecedentes: Cetuximab resulta efectivo en el carcinoma metastático o recurrente de células escamosas de cabeza y cuello, resistente al platino. Se investigó la eficacia de cetuximab más quimioterapia basada en platino como tratamiento de primera línea en pacientes con carcinoma metastático o recurrente de células escamosas de cabeza y cuello. Métodos: Se asignaron al azar 220 pacientes de 442 pacientes elegibles con carcinoma metastático o recurrente de células escamosas de cabeza y cuello sin tratamiento, para recibir cisplatino (a una dosis de 100mg por metro cuadrado de área de superficie corporal el día 1) o carboplatino (en un área por debajo de la curva de 5mg por mililitro por minuto, como infusión intravenosa de 1 hora el día 1) más fluorouracilo (a una dosis de 1000mg por metro cuadrado por día, durante 4 días) cada 3 semanas, por un máximo de 6 ciclos, y 222 pacientes para recibir la misma quimioterapia más cetuximab (a una dosis de 400mg por metro cuadrado en forma inicial, como infusión intravenosa de 2 horas, luego 250mg por metro cuadrado, como infusión intravenosa de 1 hora por semana) durante un máximo de 6 ciclos. Los pacientes con enfermedad estable que recibieron quimioterapia más cetuximab continuaron recibiendo cetuximab hasta la progresión de la enfermedad o hasta la aparición de efectos tóxicos inaceptables, lo que ocurriera primero. Resultados: El agregado de cetuximab a la quimioterapia basada en platino con fluorouracilo (platino-fluorouracilo) prolongó de manera significativa la mediana de la supervivencia global, de 7.4 meses en el grupo de quimioterapia sola a 10.1 meses en el grupo que recibía quimioterapia más cetuximab (índice de riesgo para muerte = 0.80; intervalo de confianza 95%: 0.64-0.99; p = 0.04). El agregado de cetuximab prolongó la mediana del tiempo de supervivencia libre de progresión de 3.3 meses a 5.6 meses (índice de riesgo para la progresión = 0.54; p < 0.001) y aumentó la tasa de respuesta de 20% a 36% (p < 0.001).
Assuntos
Tratamento Farmacológico , Drogas em Investigação , Neoplasias de Cabeça e Pescoço , Interpretação Estatística de DadosRESUMO
Antecedentes: Cetuximab resulta efectivo en el carcinoma metastático o recurrente de células escamosas de cabeza y cuello, resistente al platino. Se investigó la eficacia de cetuximab más quimioterapia basada en platino como tratamiento de primera línea en pacientes con carcinoma metastático o recurrente de células escamosas de cabeza y cuello. Métodos: Se asignaron al azar 220 pacientes de 442 pacientes elegibles con carcinoma metastático o recurrente de células escamosas de cabeza y cuello sin tratamiento, para recibir cisplatino (a una dosis de 100mg por metro cuadrado de área de superficie corporal el día 1) o carboplatino (en un área por debajo de la curva de 5mg por mililitro por minuto, como infusión intravenosa de 1 hora el día 1) más fluorouracilo (a una dosis de 1000mg por metro cuadrado por día, durante 4 días) cada 3 semanas, por un máximo de 6 ciclos, y 222 pacientes para recibir la misma quimioterapia más cetuximab (a una dosis de 400mg por metro cuadrado en forma inicial, como infusión intravenosa de 2 horas, luego 250mg por metro cuadrado, como infusión intravenosa de 1 hora por semana) durante un máximo de 6 ciclos. Los pacientes con enfermedad estable que recibieron quimioterapia más cetuximab continuaron recibiendo cetuximab hasta la progresión de la enfermedad o hasta la aparición de efectos tóxicos inaceptables, lo que ocurriera primero. Resultados: El agregado de cetuximab a la quimioterapia basada en platino con fluorouracilo (platino-fluorouracilo) prolongó de manera significativa la mediana de la supervivencia global, de 7.4 meses en el grupo de quimioterapia sola a 10.1 meses en el grupo que recibía quimioterapia más cetuximab (índice de riesgo para muerte = 0.80; intervalo de confianza 95%: 0.64-0.99; p = 0.04). El agregado de cetuximab prolongó la mediana del tiempo de supervivencia libre de progresión de 3.3 meses a 5.6 meses (índice de riesgo para la progresión = 0.54; p < 0.001) y aumentó la tasa de respuesta de 20% a 36% (p < 0.001).(AU)