Capacidad pronóstica del PIV (pan-immune-inflammation value) en pacientes con carcinoma escamoso de cabeza y cuello / Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma

Introducción: El PIV (pan-immune-inflammation value), un índice que resulta del cociente (neutrófilos×monocitos×plaquetas) / linfocitos, ha sido propuesto como un biomarcador con capacidad pronóstica en diferentes modelos tumorales. El objetivo del presente estudio es analizar la capacidad pronóstica del PIV en pacientes con carcinoma escamoso de cabeza y cuello. Pacientes y métodos: Estudio retrospectivo de 1.187 pacientes con carcinoma escamoso de cabeza y cuello tratados en nuestro centro durante el periodo 2000-2017. Se obtuvo el valor del PIV a partir de un análisis realizado en un intervalo inferior a las 3 semanas previas al inicio del tratamiento. Resultados: El valor del PIV se relacionó de forma significativa con el consumo de tóxicos (p=0,001), la localización del tumor (0,0001), la extensión tumoral (0,0001), y el grado histológico (0,016). Mediante un análisis de partición recursiva se definieron 4 categorías en función del valor del PIV: categoría i: PIV<136,3 (n=118; 9,9%), categoría ii: PIV 136,3-451,1 (n=594, 50,0%); categoría iii: PIV 451,1-1.141,2 (n=357; 30,1%); categoría iv: PIV>1.141,2 (n=118; 9,9%). Se pudo observar una reducción ordenada y significativa de la supervivencia específica a medida que se incrementaba la categoría en el valor del PIV. Esta disminución en la supervivencia se produjo de forma independiente al tipo de tratamiento, la extensión del tumor, o la localización del tumor primario. La categoría en el valor del PIV se relacionó de forma significativa con la supervivencia específica en un estudio multivariable. Conclusiones: El PIV es un biomarcador con capacidad pronóstica en los pacientes con carcinoma escamoso de cabeza y cuello.(AU)

Introduction: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methods: Retrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. Results: PIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. Conclusions: PIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.(AU)

Resultados oncológicos del tratamiento de rescate en pacientes con carcinomas de orofaringe tratados con radioterapia / Oncological results of salvage treatment in patients with oropharynx carcinoma treated with radiotherapy

Objetivo Evaluar las posibilidades de rescate tras la recidiva local en pacientes con carcinomas de orofaringe tratados con radioterapia y analizar los factores pronósticos relacionados con el control final de la enfermedad. Métodos Estudio retrospectivo de 596 con carcinomas de orofaringe pacientes tratados con radioterapia durante el periodo 1991-2018. Resultados Ciento ochenta y un pacientes (30,4%) tuvieron una recidiva local. De los pacientes con una recidiva local, 51 (28,2%) fueron tratados con una cirugía de rescate. Las variables que se relacionaron con que el paciente no recibiese una cirugía de rescate fueron una edad superior a los 75 años, la localización del tumor en la pared posterior de la hipofaringe, una extensión inicial del tumor cT4 y un intervalo libre de recidiva inferior a los 6 meses. La supervivencia específica a los 5 años de los pacientes tratados con una cirugía de rescate fue del 19,1% (IC del 95%: 7,3-30,9%). Las variables que se relacionaron con la supervivencia específica fueron la extensión de la recidiva y el estatus de los márgenes de resección. No se consiguió el control final del tumor en ninguno de los pacientes con una recidiva extensa (rpT3-4, n=25) o con unos márgenes de resección positivos (n=22). Conclusión Los pacientes con carcinomas de orofaringe tratados con radioterapia con una recidiva local del tumor cuentan con un pronóstico limitado. Una mayoría de los pacientes (71,8%) no fueron considerados candidatos a cirugía de rescate. La supervivencia específica a los 5 años de los pacientes tratados con una cirugía de rescate fue del 19,1%. (AU)

Objective To evaluate the possibilities of salvage after local recurrence in patients with oropharyngeal carcinomas treated with radiotherapy, and to analyze the prognostic factors related to the final control of the disease. Methods Retrospective study of 596 patients with oropharyngeal carcinoma treated with radiotherapy during the period 1991–2018. Results One hundred and eighty-one patients (30.4%) had a local recurrence. Of the patients with a local recurrence, 51 (28.2%) were treated with salvage surgery. Variables that were associated with the patient not receiving salvage surgery were age greater than 75 years, tumor location in the posterior hypopharyngeal wall, an initial tumor extent cT4, and a recurrence-free interval of less than 6 months. Five-year specific survival of patients treated with salvage surgery was 19.1% (95% CI: 7.3%–30.9%). Variables that were related to specific survival were extent of recurrence and status of resection margins. Final tumor control was not achieved in any of the patients with extensive recurrence (rpT3-4, n=25) or positive resection margins (n=22). Conclusion Patients with oropharyngeal carcinomas treated with radiotherapy with local tumor recurrence have a limited prognosis. Most patients (71.8%) were not considered candidates for salvage surgery. The 5-year specific survival of patients treated with salvage surgery was 19.1%. (AU)

External validation of the GETTEC algorithm for elective neck dissection in patients candidates for salvage total laryngectomy.

OBJECTIVE: To perform an external validation of the algorithm for elective treatment of the lymph node areas proposed by GETTEC for patients candidates to salvage total laryngectomy after radiotherapy. This algorithm is based on the initial lymph node status, local extension of the recurrence and time to recurrence. MATERIAL AND METHODS: Retrospective study performed in 151 patients treated with salvage total laryngectomy without clinical or radiological evidence of regional involvement at the time of diagnosis of recurrence (rcN0). The percentage of patients with occult lymph node metastases was calculated according to the algorithm proposed by GETTEC. RESULTS: A total of 14.6 % (n = 22) of the patients had occult lymph node metastases. Patients with locally advanced recurrences (rcT4) had a higher risk of occult lymph node metastases. There were no significant differences in the risk of occult lymph node metastases according to initial lymph node status or time to recurrence. When applying the algorithm proposed by GETTEC, there were no significant differences in the percentage of occult lymph node metastases between the group of patients who were candidates for follow-up (14.4 %) and those candidates for elective neck dissection (14.9 %) (P = 0.940). According to our results, patients who were candidates for an elective neck dissection were those with tumors located in the supraglottis or rcT4 glottic tumors. CONCLUSION: Our results do not validate the algorithm proposed by GETTEC for the management of the lymph nodes in rcN0 patients who are candidates for salvage total laryngectomy after radiotherapy.

Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma.

INTRODUCTION: The pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils × monocytes × platelets)/lymphocytes, has been proposed as a prognostic biomarker in different tumour models. The aim of this study is to analyse the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Retrospective study of 1187 patients with HNSCC treated at our centre between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. RESULTS: PIV value was significantly associated with toxic consumption (0.001), tumour location (0.0001), tumour extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category I: PIV < 136.3 (n = 118, 9.9%), category II: PIV 136.3-451.1 (n = 594, 50.0%), category III: PIV 451.1-1,141.2 (n = 357, 30.1%), and category IV: PIV > 1141.2 (n = 118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumour extension, or location of the primary tumour. The PIV category was and independent prognostic factor of disease-specific survival in a multivariable study. CONCLUSIONS: PIV is a prognostic biomarker in patients with HNSCC.

Oncological results of salvage treatment in patients with oropharynx carcinoma treated with radiotherapy.

OBJECTIVE: To evaluate the possibilities of salvage after local recurrence in patients with oropharyngeal carcinomas treated with radiotherapy, and to analyse the prognostic factors related to the final control of the disease. METHODS: Retrospective study of 596 patients with oropharyngeal carcinoma treated with radiotherapy during the period 1991-2018. RESULTS: One hundred and eighty-one patients (30.4%) had a local recurrence. Of the patients with a local recurrence, 51 (28.2%) were treated with salvage surgery. Variables that were associated with the patient not receiving salvage surgery were age greater than 75 years, tumour location in the posterior hypopharyngeal wall, an initial tumour extent cT4, and a recurrence-free interval of less than 6 months. Five-year specific survival of patients treated with salvage surgery was 19.1% (95% CI: 7.3%-30.9%). Variables that were related to specific survival were extent of recurrence and status of resection margins. Final tumour control was not achieved in any of the patients with extensive recurrence (rpT3-4, n = 25) or positive resection margins (n = 22). CONCLUSION: Patients with oropharyngeal carcinomas treated with radiotherapy with local tumour recurrence have a limited prognosis. Most patients (71.8%) were not considered candidates for salvage surgery. The 5-year specific survival of patients treated with salvage surgery was 19.1%.

Segundas neoplasias esofágicas tras un tumor índice de cabeza y cuello: incidencia, factores de riesgo y pronóstico / Second esophageal neoplasms after head and neck index tumor: Incidence, risk factors and prognosis

Objetivo Los pacientes con un carcinoma escamoso de cabeza y cuello (CECC) tienen un riesgo incrementado de aparición de segundas neoplasias esofágicas. El objetivo del presente estudio es evaluar la incidencia de aparición, los factores de riesgo y el pronóstico de las segundas neoplasias esofágicas en los pacientes con un CECC. Material y métodos Realizamos un estudio retrospectivo en 4.711 pacientes con un tumor índice localizado en la cavidad oral, orofaringe, hipofaringe o laringe durante el periodo 1985-2020.ResultadosDurante el periodo analizado 149 pacientes (3,2%) presentaron una segunda neoplasia esofágica. La incidencia de segunda neoplasia esofágica fue del 0,42% anual y se mantuvo prácticamente constante a lo largo del periodo de seguimiento analizado. De acuerdo con el resultado del estudio multivariante, los factores de riesgo relacionados con la aparición de segundas neoplasias esofágicas fueron: el antecedente de un consumo elevado de alcohol y la localización del tumor primario en la orofaringe o la hipofaringe. La supervivencia específica a los 5 años para los pacientes con una segunda neoplasia de esófago, calculada a partir del diagnóstico de esta segunda neoplasia, fue del 10,5%. Conclusiones Los pacientes con un CECC tienen un riesgo incrementado de sufrir la aparición de una segunda neoplasia esofágica. Los factores de riesgo asociados con la aparición de una segunda neoplasia esofágica fueron el consumo severo de alcohol y la localización del tumor primario en la orofaringe o la hipofaringe. (AU)

Objective Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of second esophageal neoplasms. The aim of the present study is to evaluate the incidence, risk factors and prognosis of second esophageal neoplasms in patients with HNSCC. Material and methods A retrospective study of 4,711 patients with index tumor in the oral cavity, oropharynx, hypopharynx or larynx between 1985 and 2020 was conducted. Results During the period analyzed 149 patients (3.2%) had a second esophageal neoplasm. The incidence of second esophageal neoplasia was 0.42% per year and remained nearly constant throughout the follow-up period. According to the results of a multivariate study, the risk factors related to the appearance of second esophageal neoplasms were a history of high alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx. The 5-year disease-specific survival rate in patients with a second esophageal neoplasm, calculated from the diagnosis of this second neoplasm, was 10.5%. Conclusions Patients with a HNSCC have an increased risk of developing of a second esophageal neoplasm. The risk factors associated with the appearance of a second esophageal neoplasm were severe alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx. (AU)

¿Está justificado hacer un screening a largo plazo para el cáncer de pulmón en los pacientes con un carcinoma de cabeza y cuello? / Is long-term screening for lung cancer justified in patients with head and neck carcinoma?

Objetivo Los pacientes con un carcinoma escamoso de cabeza y cuello (CECC) tienen un mayor riesgo de aparición de segundas neoplasias localizadas en el pulmón que la población general. El objetivo del presente estudio es evaluar la incidencia a largo plazo de segundas neoplasias pulmonares tras el diagnóstico de un CECC y considerar la conveniencia de la realización de un cribado de cáncer de pulmón en estos pacientes. Material y métodos Realizamos un estudio retrospectivo en 4.954 pacientes con un tumor índice localizado en la cavidad oral, orofaringe, hipofaringe o laringe durante el periodo 1985-2017. Resultados Durante el periodo de seguimiento 469 pacientes (9,5%) presentaron una segunda neoplasia pulmonar. La incidencia de segunda neoplasia pulmonar fue del 1,26% anual, y se mantuvo prácticamente constante a lo largo de los 25 años de seguimiento analizados. Según los resultados de un estudio multivariante, los pacientes varones, con edades comprendidas entre los 50 y los 80 años, con antecedentes de tabaquismo y con tumores localizados en la orofaringe o en la supraglotis fueron los que presentaron un mayor riesgo de segunda neoplasia pulmonar. Conclusiones Los pacientes con un CECC como tumor índice tienen un alto riesgo de segundas neoplasias localizadas en el pulmón. Para conseguir un diagnóstico precoz de estas segundas neoplasias sería conveniente establecer protocolos de cribado basados en el uso de la TAC pulmonar de baja dosis, que deberían mantenerse indefinidamente durante el periodo de seguimiento. (AU)

Objective Patients with head and neck squamous cell carcinoma (HNSCC) have a higher risk of second lung neoplasms than the general population. The aim of the present study is to evaluate the long-term incidence of second lung malignancies after the diagnosis of a HNSCC and to consider the convenience of the screening for lung cancer in these patients. Material and methods We conducted a retrospective study performed on 4,954 patients with an index tumor located in the oral cavity, oropharynx, hypopharynx, or larynx during the period 1985-2017. Results During the follow-up period 469 patients (9.5%) presented a second pulmonary neoplasm. The incidence of second lung neoplasm was 1.26% per year and remained practically constant throughout the 25-year follow-up period analyzed. According to the results of a multivariate study, male patients, aged between 50 and 80 years, with a history of tobacco use, and with tumors located in the oropharynx or the supraglottis were those with the highest risk of second lung neoplasms. Conclusion Patients with a HNSCC index tumor have a high risk of second neoplasms located in the lung. In order to achieve an early diagnosis of these second neoplasms, it would be advisable to establish screening protocols based on the use of low-dose lung CT, which should be maintained indefinitely during the follow-up period. (AU)

Second esophageal neoplasms after head and neck index tumor: Incidence, risk factors and prognosis.

OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of second esophageal neoplasms. The aim of the present study is to evaluate the incidence, risk factors and prognosis of second esophageal neoplasms in patients with HNSCC. METHODS: A retrospective study of 4711 patients with index tumor in the oral cavity, oropharynx, hypopharynx or larynx between 1985 and 2020 was conducted. RESULTS: During the period analysed 149 patients (3.2%) had a second esophageal neoplasm. The incidence of second esophageal neoplasia was 0.42% per year and remained nearly constant throughout the follow-up period. According to the results of a multivariate study, the risk factors related to the appearance of second esophageal neoplasms were a history of high alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx. The 5-year disease-specific survival rate in patients with a second esophageal neoplasm, calculated from the diagnosis of this second neoplasm, was 10.5%. CONCLUSIONS: Patients with a HNSCC have an increased risk of developing of a second esophageal neoplasm. The risk factors associated with the appearance of a second esophageal neoplasm were severe alcohol consumption and the location of the primary tumor in the oropharynx or hypopharynx.

Differential characteristics of patients with squamous cell carcinoma of the head and neck with no history of tobacco or alcohol use.

OBJECTIVE: The present study aims to analyse the differential characteristics of patients with head and neck squamous cell carcinoma (HNSCC) without a history of consumption of toxic substances such as tobacco and alcohol. MATERIAL AND METHODS: We carried out a retrospective study of 4694 patients with HNSCC located in the oral cavity, oropharynx, hypopharynx or larynx treated in our centre during the period 1985-2019. RESULT: 7.7% of the patients (n = 363) did not report a history of consumption of toxic substances. The group of patients with no toxic history was older, had a higher proportion of women, a higher frequency of cases located in the oral cavity, a higher proportion of cases diagnosed in early stages, and a lower incidence of second neoplasms. The percentage of patients with no history of consumption of toxic substances increased significantly over the study period. The overall survival of patients with no history of consumption of toxic substances was significantly higher than that of patients with toxic substances use. Specific survival for patients with tumours located in the oral cavity without a history of consumption of toxic substances was significantly lower than that of patients with toxic substances use, whereas for patients with oropharyngeal carcinomas the absence of a history of consumption of toxic substances was associated with a better prognosis. CONCLUSIONS: There were differences in the epidemiological and prognostic characteristics of patients with HNSCC according to the history of consumption of toxic substances such as tobacco and alcohol.

Características diferenciales de los pacientes con carcinoma escamoso de cabeza y cuello sin antecedentes de consumo de tabaco ni alcohol / Differential characteristics of patients with squamous cell carcinoma of the head and neck with no history of tobacco or alcohol use

Objetivo: El objetivo del presente estudio es analizar las características diferenciales de los pacientes con un carcinoma escamoso de cabeza y cuello (CECC) sin antecedentes de consumo de tóxicos, como el tabaco y el alcohol.Material y métodosSe llevó a cabo un estudio retrospectivo de 4.694 pacientes con un CECC localizado en la cavidad oral, orofaringe, hipofaringe o laringe tratados en nuestro centro durante el periodo 1985-2019.ResultadoUn 7,7% de los pacientes (n=363) no refirieron el antecedente de consumo de tóxicos. El grupo de pacientes sin antecedentes tóxicos tenía mayor edad, una mayor proporción de mujeres, una mayor frecuencia de casos localizados en la cavidad oral, una mayor proporción de casos diagnosticados en estadios iniciales y una menor incidencia de segundas neoplasias. El porcentaje de pacientes sin antecedentes de consumo de tóxicos aumentó de forma significativa a lo largo del periodo de estudio. La supervivencia global de los pacientes sin antecedentes de consumo de tóxicos fue significativamente más elevada que la de los pacientes con antecedentes tóxicos. La supervivencia específica para los pacientes con tumores localizados en la cavidad oral sin antecedentes tóxicos fue significativamente inferior, en tanto que para los pacientes con carcinomas de orofaringe la ausencia de antecedentes de consumo de tóxicos se asoció a un mejor pronóstico.ConclusionesExistieron diferencias en las características epidemiológicas y pronósticas de los pacientes con CECC en función del antecedente de consumo de tóxicos como el tabaco o el alcohol. (AU)

Objective: The present study aims to analyze the differential characteristics of patients with head and neck squamous cell carcinoma (HNSCC) without a history of consumption of toxic substances such as tobacco and alcohol.Material and methodsWe carried out a retrospective study of 4,694 patients with HNSCC located in the oral cavity, oropharynx, hypopharynx or larynx treated in our center during the period 1985-2019.ResultThe 7.7% of the patients (n=363) did not report a history of consumption of toxic substances. The group of patients with no toxic history was older, had a higher proportion of women, a higher frequency of cases located in the oral cavity, a higher proportion of cases diagnosed in early stages, and a lower incidence of second neoplasms. The percentage of patients with no history of consumption of toxic substances increased significantly over the study period. The overall survival of patients with no history of consumption of toxic substances was significantly higher than that of patients with toxic substances use. Specific survival for patients with tumors located in the oral cavity without a history of consumption of toxic substances was significantly lower than that of patients with toxic substances use, whereas for patients with oropharyngeal carcinomas the absence of a history of consumption of toxic substances was associated with a better prognosis.ConclusionsThere were differences in the epidemiological and prognostic characteristics of patients with HNSCC according to the history of consumption of toxic substances such as tobacco and alcohol. (AU)

Is long-term screening for lung cancer justified in patients with head and neck carcinoma?

OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) have a higher risk of second lung neoplasms than the general population. The aim of the present study is to evaluate the long-term incidence of second lung malignancies after the diagnosis of a HNSCC and to consider the convenience of the screening for lung cancer in these patients. MATERIAL AND METHODS: We conducted a retrospective study performed on 4954 patients with an index tumor located in the oral cavity, oropharynx, hypopharynx, or larynx during the period 1985-2017. RESULTS: During the follow-up period 469 patients (9.5%) presented a second pulmonary neoplasm. The incidence of second lung neoplasm was 1.26% per year and remained practically constant throughout the 25-year follow-up period analyzed. According to the results of a multivariate study, male patients, aged between 50 and 80 years, with a history of tobacco use, and with tumors located in the oropharynx or the supraglottis were those with the highest risk of second lung neoplasms. CONCLUSION: Patients with a HNSCC index tumor have a high risk of second neoplasms located in the lung. In order to achieve an early diagnosis of these second neoplasms, it would be advisable to establish screening protocols based on the use of low-dose lung CT, which should be maintained indefinitely during the follow-up period.

Case report: De novo pathogenic variant in WFS1 causes Wolfram-like syndrome debuting with congenital bilateral deafness.

Background: Congenital deafness could be the first manifestation of a syndrome such as in Usher, Pendred, and Wolfram syndromes. Therefore, a genetic study is crucial in this deficiency to significantly improve its diagnostic efficiency, to predict the prognosis, to select the most adequate treatment required, and to anticipate the development of other associated clinical manifestations. Case presentation: We describe a young girl with bilateral congenital profound deafness, who initially received a single cochlear implant. The genetic study of her DNA using a custom-designed next-generation sequencing (NGS) panel detected a de novo pathogenic heterozygous variant in the WFS1 gene related to Wolfram-like syndrome, which is characterized by the presence of other symptoms such as optic atrophy. Due to this diagnosis, a second implant was placed after the optic atrophy onset. The speech audiometric results obtained with both implants indicate that this work successfully allows the patient to develop normal speech. Deterioration of the auditory nerves has not been observed. Conclusion: The next-generation sequencing technique allows a precise molecular diagnosis of diseases with high genetic heterogeneity, such as hereditary deafness, while this was the only symptom presented by the patient at the time of analysis. The NGS panel, in which genes responsible for both syndromic and non-syndromic hereditary deafness were included, was essential to reach the diagnosis in such a young patient. Early detection of the pathogenic variant in the WFS1 gene allowed us to anticipate the natural evolution of the disease and offer the most appropriate management to the patient.

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy

FNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients.MethodsWe determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III–IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis.ResultsThere were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5–49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2–100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71–22.06).ConclusionFNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival. (AU)

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy.

PURPOSE: FNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients. METHODS: We determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III-IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis. RESULTS: There were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5-49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2-100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71-22.06). CONCLUSION: FNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival.

Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy.

PURPOSE: Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. METHODS: We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). RESULTS: During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2-60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5-81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22-4.10, P = 0.009). CONCLUSION: Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.

Causes of long-term mortality in patients with head and neck squamous cell carcinomas.

PURPOSE: After treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. METHODS: We carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. RESULTS: After the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. CONCLUSION: There are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness.

In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan.

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at http://sbi.upf.edu/data/tpms/.

Surgical options in benign parotid tumors: a proposal for classification.

Different surgical options are currently available for treating benign tumors of the parotid gland, and the discussion on optimal treatment continues despite several meta-analyses. These options include more limited resections (extracapsular dissection, partial lateral parotidectomy) versus more extensive and traditional options (lateral parotid lobectomy, total parotidectomy). Different schools favor one option or another based on their experience, skills and tradition. This review provides a critical analysis of the literature regarding these options. The main limitation of all the studies is the bias of selection for different surgical approaches. For this reason, we propose a staging system that could facilitate clinical decision making and the comparison of results. We propose four categories based on the size of the tumor and its location within the parotid gland. Category I includes tumors up to 3 cm, which are mobile, close to the outer surface and close to the parotid borders. Category II includes deeper tumors up to 3 cm. Category III comprises tumors greater than 3 cm involving two levels of the parotid gland, and category IV tumors are greater than 3 cm and involve more than 2 levels. For each category and for the various pathologic types, a guideline of surgical extent is proposed. The objective of this classification is to facilitate prospective multicentric studies on surgical techniques in the treatment of benign parotid tumors and to enable the comparison of results of different clinical studies.

Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology), we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

Methods for diagnosing perceived age on the basis of an ensemble of phenotypic features.

BACKGROUND: Perceived age has been defined as the age that a person is visually estimated to be on the basis of physical appearance. In a society where a youthful appearance are an object of desire for consumers, and a source of commercial profit for cosmetic companies, this concept has a prominent role. In addition, perceived age is also an indicator of overall health status in elderly people, since old-looking people tend to show higher rates of morbidity and mortality. However, there is a lack of objective methods for quantifying perceived age. METHODS: In order to satisfy the need of objective approaches for estimating perceived age, a novel algorithm was created. The novel algorithm uses supervised mathematical learning techniques and error retropropagation for the creation of an artificial neural network able to learn biophysical and clinically assessed parameters of subjects. The algorithm provides a consistent estimation of an individual's perceived age, taking into account a defined set of facial skin phenotypic traits, such as wrinkles and roughness, number of wrinkles, depth of wrinkles, and pigmentation. A nonintervention, epidemiological cross-sectional study of cases and controls was conducted in 120 female volunteers for the diagnosis of perceived age using this novel algorithm. Data collection was performed by clinical assessment of an expert panel and biophysical assessment using the ANTERA 3D(®) device. RESULTS AND DISCUSSION: Employing phenotype data as variables and expert assignments as objective data, the algorithm was found to correctly classify the samples with an accuracy of 92.04%. Therefore, we have developed a method for determining the perceived age of a subject in a standardized, consistent manner. Further application of this algorithm is thus a promising approach for the testing and validation of cosmetic treatments and aesthetic surgery, and it also could be used as a screening method for general health status in the population.