Quality of life, adherence to voice rehabilitation therapy and psychological variables in patients with head and neck cancer / Calidad de vida, adherencia al tratamiento de rehabilitación de voz y variables psicológicas en pacientes con cáncer de cabeza y cuello

Introduction: Voice problems can affect quality of life (QoL), other psychological aspects, and the adequate adherence to voice rehabilitation therapy. Objective: To determine the association between QoL and treatment adherence (TA) to voice rehabilitation with symptoms of anxiety, depression, and coping strategies. Method: A longitudinal study was conducted with 97 participants with head and neck cancer (H&N) who were attending voice rehabilitation therapy. Instruments: EORTC QLQ-C30 and QLQ-H&N35, Treatment Adherence Checklist, Cancer Coping Questionnaire and HADS. Results: The mean overall QoL was 83.33, and mean TA was 8.80. Lower overall QoL and emotional functioning scores, as well as higher dry mouth scores were associated with higher levels of anxiety. Greater problems with social contact and lower TA were associated to higher depression scores. Conclusion: Consistent with the literature, TA and QoL were associated to depression and QoL was also correlated to anxiety. These results are among the first to explore such aspects in Latino patients and emphasize the importance of multidisciplinary care for H&N cancer patients in voice rehabilitation therapy, given that during their treatment they may encounter psychological barriers that could hinder their progress in voice quality and QoL.(AU)

Introducción: Los problemas de la voz pueden afectar la calidad de vida (CV) y otros aspectos psicológicos, así como la adecuada adherencia a la terapia de rehabilitación de voz. Objetivo: Determinar la relación entre la CV y la adherencia al tratamiento (AT) de rehabilitación de voz con síntomas de ansiedad, depresión y estrategias de afrontamiento. Método: Se realizó un estudio longitudinal en 97 participantes con cáncer de cabeza y cuello (CyC) que asistían a terapia de rehabilitación de voz. Instrumentos: EORTC QLQ-C30 y QLQ-H&N35, Lista de Verificación de Adherencia al Tratamiento, la Escala de Afrontamiento al Cáncer y la HADS. Resultados: La CV global promedio fue de 83.33 y el puntaje promedio de AT fue de 8.80. La calidad de vida global, la función emocional y boca seca se asociaron con la ansiedad. La dimensión de la CV contacto social y la AT tuvieron relación con la depresión. Conclusiones: Consistente con la literatura la AT y la CV tuvieron relación con la depresión y solo la CV se relacionó con la ansiedad. Los resultados presentados son de los primeros en explorar estos aspectos en pacientes latinos y enfatizan la importancia de la atención multidisciplinaria a pacientes con cáncer de CyC en terapia de rehabilitación de voz, dado que en el curso de sus tratamientos pueden encontrar barreras psicológicas que obstaculicen la mejora en la calidad de la voz y la CV.(AU)

Has the 8th American joint committee on cancer TNM staging improved prognostic performance in oral cancer? A systematic review / ¿Ha mejorado la estadificación TNM del octavo comité conjunto estadounidense sobre cáncer? ¿Rendimiento pronóstico en el cáncer oral? Una revisión sistemática

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) classification has introduced two new parameters: depth of invasion (DOI) and extranodal extension (ENE). The aim of this systematic review was to determine whether this 8th edition referred to oral squamous cell carcinoma (OSCC) offers performance superior to that of the 7th edition in relation to overall survival (OS) and disease-specific survival (DSS). Material and Methods: The review was carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed (MEDLINE), Scopus and Cochrane Library databases were searched covering the period up until April 7th, 2022.Results: Thirteen retrospective cohort studies were finally included. The introduction of DOI and ENE in the 8th edition of the AJCC classification resulted in improved prognostic performance of the classification. Conclusions: Patients with OSCC can be better classified in relation to OS and DSS, while maintaining the simplicity and ease of use of the classification. This allows more appropriate treatment protocols to be applied and affords a better estimation of the prognosis of each patient.(AU)

Risk factors for oral mucositis in patients with solid tumorsunder treatment with cetuximab: a retrospective cross-sectional study

Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. Material and Methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). Results: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. Conclusions: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution. (AU)

Valor pronóstico de los parámetros hematológicos y los parámetros metabólicos de la PET/TC con [18F]FDG en el cáncer de cabeza y cuello / Prognostic value of haematological parameters and [18F]FDG PET/CT metabolic parameters in head and neck cancer

Objetivo Determinar la utilidad de los cocientes neutrófilos/linfocitos (N/L) y plaquetas/linfocitos (P/L), así como de parámetros cuantitativos de la PET/TC con [18F]FDG, como factores pronósticos para la supervivencia global (SG), la supervivencia cáncer específica (SCE) y la supervivencia libre de progresión (SLP) en pacientes con carcinoma escamoso de cabeza y cuello (CyC) Material y métodos Se valoraron retrospectivamente 66 pacientes (56 hombres) diagnosticados de CyC durante un intervalo de 8años. Se determinaron los parámetros SUV máximo (SUVmax), volumen metabólico tumoral (MTV) y glucólisis tumoral total (TLG) del estudio PET/TC al diagnóstico. Tras tratamiento con quimiorradioterapia, se valoró la supervivencia de los pacientes. El modelo de regresión de Cox y el método de Kaplan-Meier se utilizaron para analizar factores pronósticos y curvas de supervivencia. Resultados El seguimiento medio fue de 50,4meses, produciéndose 39 recurrencias-progresiones y 39 fallecimientos. En el análisis univariante los parámetros metabólicos, excepto el SUVmax, fueron factores predictivos para las tres supervivencias, y los dos parámetros sanguíneos lo fueron para la SG y la SCE. La TLG fue el único factor predictivo en el análisis multivariante. Las tres curvas de supervivencias fueron significativamente diferentes para los parámetros metabólicos y la curva de SG para el cociente N/L. Se apreciaron correlaciones entre el cociente N/L, el MTV y la TLG. No se demostraron correlaciones entre el cociente P/L y los parámetros metabólicos. Conclusión El uso de marcadores hematológicos y metabólicos permitiría identificar pacientes con un alto riesgo de recurrencias y pobre supervivencia e individualizar el tratamiento aplicando terapias más agresivas (AU)

Aim To determine the usefulness of neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios as well as quantitative [18F]FDG PET/CT parameters as prognostic factors for overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) in patients with head and neck squamous cell carcinoma (HyN). Material and methods Sixty-six patients (56 men) diagnosed with HyN carcinoma were retrospectively assessed over an 8-year interval. Maximum SUV (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) parameters were determined from the PET/CT study at diagnosis. After treatment with chemoradiotherapy, patient survival was assessed. The Cox regression model and the Kaplan-Meier method were used to analyse prognostic factors and survival curves. Results Median follow-up was 50.4months, with 39 recurrences-progressions and 39 deaths. In the univariate analysis, metabolic parameters, except SUVmax, were predictive factors for all three survivals and the two blood parameters were predictive for OS and EFS. TLG was the only predictive factor in the multivariate analysis. The three survival curves were significantly different for the metabolic parameters and the OS curve for the N/L ratio. Correlations were seen between N/L ratio, MTV and TLG. No correlations were demonstrated between P/L ratio and metabolic parameters. Conclusion The use of haematological and metabolic markers would allow to identify patients with a high risk of recurrences and poor survival and to individualise treatment by applying more aggressive therapies (AU)

Status of head and neck brachytherapy in Spain in 2022

Purpose Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. Methods The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. Results The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. Conclusion It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists (AU)

Polimorfismos genéticos asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab / Genetic polymorphisms associated with the response of head and neck carcinoma to cetuximab

Objetivo: Exponer los principales polimorfismos genéticos que han sido asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab. Método: Se realizó una revisión no exhaustiva de artículos publicados en el período de enero de 2000 a diciembre de 2022, para ello se emplearon las bases de datos Medline (vía Pubmed) y Science Direct. En la evaluación de la calidad metodológica de los artículos incluidos se utilizó la guía para los estudios de asociación genética (Q-Genie). Resultados: Se identificaron un total de 206 artículos, de los cuales 12 cumplieron con los criterios para el análisis final. Se reportaron varios polimorfismos, tales como: EGFR-R521K (AA/GA), FcγRIIIa (158VV) y FcγRIIa (131HH), KRASLCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 en sus variantes mutadas, HIF-1α (CT/TT) y XRCC5 (GG/AA) que se asociaron con las variables de supervivencia, riesgo de progresión, tiempos hasta la progresión de la enfermedad, así como toxicidad cutánea. Conclusiones: Varios polimorfismos pueden asociarse con la respuesta del carcinoma de cabeza y cuello al tratamiento con cetuximab, siendo EGFR-R521K y FcγR IIIa-V158F los más estudiados. La enorme incertidumbre de los resultados alcanzados no permite alcanzar conclusiones firmes sobre la influencia de los polimorfismos genéticos en la respuesta al cetuximab; sin embargo, pueden convertirse en biomarcadores farmacogenéticos en la práctica clínica como una valiosa herramienta en la medicina personalizada, para predecir la respuesta medicamentosa. Para ello se requiere la realización de ensayos controlados con estratos por genotipo, con asignación aleatoria del tratamiento y el análisis de otras variables con valor pronóstico conocido.(AU)

Objective: To present the main genetic polymorphisms that have been associated with the response of head and neck carcinoma to cetuximab. Method: A non-exhaustive review of articles published in the period from January 2000 to December 2022 was carried out, for this purpose the Medline (via Pubmed) and Science Direct databases were used. The guide for genetic association studies (Q-Genie) was used to evaluate the methodological quality of the included articles. Results: A total of 206 articles were identified, of which 12 met the criteria for the final analysis. Several polymorphisms were reported, such as: EGFR-R521K (AA/GA), FcγRIIIa (158VV) and FcγRIIa (131HH), KRAS-LCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 in its mutated variants, HIF- 1α (CT/TT) and XRCC5 (GG/AA) that were associated with survival variables, risk of progression, times to disease progression, as well as skin toxicity. Conclusions: Several polymorphisms can be associated with the response of head and neck carcinoma to treatment with cetuximab, being EGFR-R521K and FcγR IIIa-V158F the most studied. The enormous uncertainty of the results obtained does not allow firm conclusions to be reached about the influence of genetic polymorphisms on the response to cetuximab; however, they can become pharmacogenetic biomarkers in clinical practice as a valuable tool in personalized medicine, to predict drug response. This requires carrying out controlled trials with strata by genotype, with random assignment of treatment and the analysis of other variables with known prognostic value.(AU)

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)

Reactive cutaneous capillary endothelial proliferation predicted the efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP), a special adverse event (AE) only observed in patients treated with camrelizumab, was reported to be correlated with the efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. This study to analyze the possible correlation between the occurrence of RCCEP and efficacy of camrelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Material and Methods: In this study, we retrospectively analyzed the efficacy and RCCEP occurrence of camrelizumab in 58 patients with R/M HNSCC in the Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University School of Medicine between January 2019 and June 2022. Kaplan-Meier analysis was used to assess the correlation between the occurrence of RCCEP and the survival of enrolled patients, and COX multifactor analysis was adopted to evaluate associated factors that affected the efficacy of camrelizumab immunotherapy. Results: A significant correlation between the incidence of RCCEP and a higher objective response rate was observed in this study (p=0.008). The occurrence of RCCEP was associated with better median overall survival (17.0 months vs. 8.7 months, p<0.0001, HR=5.944, 95% CI:2.097-16.84) and better median progression-free survival (15.1 months vs. 4.0 months, p<0.0001, HR=4.329,95% CI:1.683-11.13). In COX multifactor analysis, RCCEP occurrence was also an independent prognostic factor affecting OS and PFS in patients with R/M HNSCC. Conclusions: The occurrence of RCCEP can show a better prognosis, it could be used as a clinical biomarker to predict the efficacy of camrelizumab treatment. (AU)

Rol de los cuidados perioperatorios guiados por protocolo para mejorar la recuperación tras la cirugía de cáncer de cabeza y cuello: experiencia institucional / Role of protocol-guided perioperative care to enhance recovery after head and neck neoplasm surgery: An institutional experience

Antecedentes: Enhanced recovery after surgery (ERAS) mejora la recuperación tras la cirugía. El objetivo de este estudio fue determinar si ERAS causa una reducción de la estancia hospitalaria y mejora la recuperación funcional global tras la cirugía de cáncer de cabeza y cuello. Métodos Realizamos un estudio prospectivo de control de casos histórico tras la aplicación de ERAS. La base de datos del hospital seleccionó 50 pacientes elegibles confirmados para el grupo control no ERAS, incluyéndose prospectivamente 54 pacientes en el grupo ERAS. El resultado primario fue el tiempo transcurrido hasta la disposición al alta (TRD), siendo los resultados secundarios la duración de la estancia hospitalaria (DEH), la tasa de reingreso de hasta 30 días y la puntuación QoR-15 (Quality of recovery). Los datos fueron comparados mediante pruebas paramétricas y no paramétricas adecuadas. Resultados Los datos demográficos basales de los pacientes fueron comparables entre ambos grupos. Los pacientes del grupo ERAS reflejaron un TRD significativamente más breve, en comparación con el grupo no ERAS: 8 (6-10) frente a 11 (8-16); p=0,002. La DEH fue también significativamente más corta en el grupo ERAS en comparación con el grupo no ERAS (8 [7-11] frente a 12 [9-17]; valor p=0,002). El reingreso en el plazo de 30 días no fue diferente, con una cifra de 6 pacientes en cada grupo. La puntuación QoR-15 fue estadísticamente mejor en el grupo ERAS (94,88±12,50) en comparación con el grupo no ERAS (85,44±12,68; p <0,001). Conclusión La implementación del programa ERAS redujo el TRD y la DEH, mejorando la puntuación QoR-15 sobre el resultado de la recuperación reportado por el paciente en las cirugías de cáncer de cabeza y cuello. (AU)

Background: Enhanced recovery after surgery (ERAS) improve recovery after surgery. This study aimed to determine whether ERAS leads to a decrease in stay in the hospital and improves global and functional recovery after head and neck neoplasms surgery. Methods We performed a prospective case and historical control study after the ERAS application. The hospital database selected 50 confirmed eligible patients in control non-ERAS group. Prospectively 54 patients were included in the ERAS group. The primary outcome was time to readiness for discharge (TRD); secondary outcomes were the length of stay (LOS), readmission rate of up to 30 days and Quality of recovery score QoR-15. Data were compared with appropriate parametric and nonparametric tests. Results Baseline demographic data of patients were comparable between the two groups. Patients in ERAS group had significantly shorter TRD compared to the non-ERAS group 8 (6-10) versus 11 (8-16); P=.002. LOS was also significantly shorter in the ERAS group compared to the non-ERAS group (8 [7-11] versus 12 [9-17]; P=.002). Readmission at 30-days was no different, with six patients in each group. QoR-15 score was statistically better in ERAS group (94.88±12.50) compared to non-ERAS group (85.44±12.68; P<.001). Conclusion Implementing the ERAS programme decreased TRD and LOS and improved patient-reported recovery outcome QoR-15 in head and neck neoplasms surgery. (AU)

Quality of life and nutritional status of a group of post-operative head and neck cancer patients / Calidad de vida y estado nutricional en un grupo de pacientes tras cirugía de cáncer de cabeza y cuello

Introduction: scientific evidence on the appropriate nutritional support in the treatment of post-operative head and neck cancer (HNC) patients is still limited. Objectives: our aim was to evaluate nutritional status and quality of life in HNC patients in post-operative phase with different nutritional support. Methods: fifty-four HNC patients (26 with enteral nutrition [EN] via percutaneous endoscopic gastrostomy [PEG] and 28 with oral nutrition [ON]) were included. Nutritional status was evaluated with biochemical parameters and quality of life through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: ON patients reported significantly (p < 0.05) lower levels of hemoglobin, lymphocytes, iron, folic acid, and vitamin D than EN patients, with greater percentage of ON patients found to be below the reference limits for hemoglobin (21.4 % vs 19.4 %), and significantly for serum iron (17.9 % vs 0 %) and vitamin D (78.6 % vs 30.8 %). Furthermore, EN patients had a better quality of life (63.8 ± 17.6) than ON (55.4 ± 20.3), although ON patients reported less symptoms related to dyspnea (-5.8 %), loss of appetite (-11.3 %) and vomiting (-23.1 %). Conclusions: these results suggest that the use of EN in post-operative HNC patients could have a positive effect on the nutritional status and quality of life of these patients. However, further research is needed to optimize the nutritional support in these patients in order to avoid malnutrition and improve their well-being. (AU)

Introducción: la evidencia científica sobre el soporte nutricional más apropiado en pacientes con cáncer de cabeza y cuello (CCC) en el periodopostoperatorio es aún limitada.Objetivos: el objetivo de este estudio fue evaluar el estado nutricional y la calidad de vida en pacientes con CCC en el periodo postoperatorio.Métodos: se incluyeron 54 pacientes con CCC (26 con nutrición enteral [NE] mediante gastrostomía endoscópica percutánea [PEG] y 28 connutrición oral NO]). El estado nutricional se evaluó mediante parámetros bioquímicos y la calidad de la vida, con el cuestionario European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).Resultados: los pacientes con NO reportaron valores significativamente (p < 0,05) menores de hemoglobina, linfocitos, hierro sérico, ácidofólico y vitamina D respecto a los pacientes con NE, con un mayor porcentaje de pacientes con NO por debajo de los límites de referencia dehemoglobina (21,4 % vs. 19,4 %) y significativamente de hierro sérico (17,9 % vs. 0 %) y vitamina D (78,6 % vs. 30,8 %). Además, los pacientescon NE reportaron una mejor calidad de vida (63,8 ± 17,6) respecto los pacientes con NO (55,4 ± 20,3), aunque los pacientes con NO refirieronmenos síntomas cómo disnea (-5,8 %), pérdida de apetito (-11,3 %) y vómitos (-23,1 %).Conclusión: estos resultados sugieren que el uso de NE en pacientes con HNC tras cirugía podría tener un efecto positivo sobre su estadonutricional y su calidad de vida. Sin embargo, es necesario seguir investigando para optimizar el soporte nutricional en estos pacientes a fin deevitar la desnutrición y mejorar su bienestar. (AU)

Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer

Introduction Patients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response. Materials and methods We evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs). Results Early and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%. Conclusions Anti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT (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)

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)

Psychological impact after treatment in patients with head and neck cancer

Background: Cancer is the second cause of death all over the world and it causes considerable morbidity, disability, and treatment sequela, which often lead to post-treatment pain and disfigurement. This study aims to evaluate such physical sequelae, and their psychological, (cognitive and emotional), impact, in a cohort of patients treated for Head and Neck (HNC) cancer, in search for methods to help such patients deal effectively with the psychological effects of their cancer treatments adverse consequences. Material and methods: The sample consists of 56 subjects, 47 men and 9 women, ranging from 47 years to 86 years of age, who were treated for head and neck cancers at Spanish Public General Hospital in the Otolaryngology Unit, Surgery Section. Two types of questionnaires were used in the study: the Questionnaire of Sequelae after Treatment of head and neck carcinoma and the State-Trait Anxiety Inventory (STAI-E and R). Results: With respect to anxiety, the study found high levels of state anxiety which was significantly associated with the degree of perception of social stigma but was not associated with the post-treatment sequelae themselves nor with the level of discomfort that such symptomatic sequelae produced. The presence of a post-surgical stoma with cannula, increased patient's stigma (both components: external rejection and self-rejection) and state anxiety ratings, while there was no difference in state anxiety between cannulated and non-cannulated patients. There are few differences between men and women in terms of the presence of anxiety and their responses are similar in terms of the after-effects of surgery. Conclusions: Our study confirmed that current treatments for Head and Neck carcinoma generate adverse symptomatic sequela that impose significant psychological and physical burden for these patients. We will discuss the various pathways for preventive intervention that these findings open up. (AU)

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis

Background: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. Material and methods: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". Results: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. Conclusions: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test. (AU)

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. Material and methods: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. Results: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. Conclusions: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC. (AU)

Thyroglossal duct cyst carcinoma case series-Management strategy and outcomes / Serie de casos de carcinoma del conducto tirogloso: estrategias de tratamiento y resultados

Objective: To review the clinical presentation, diagnosis, pathology and management strategies in a modern cohort of patients with thyroglossal duct cyst carcinoma. Study design: Retrospective case series following PROCESS Guidelines. Setting Comprehensive cancer centre. Methods: Data recorded included: gender, age at diagnosis, clinical presentation, thyroid function, diagnostic investigations, cytological results, final histology, staging and follow up status. The risk of malignancy in cytological analysis was stratified according to the Royal College of Pathologists classification in United Kingdom. Results: Twelve patients were included. The majority of patients (66.7%) presented with an isolated thyroglossal duct cyst. Only 4 patients had preoperative cytological suspicion of carcinoma (sensitivity: 33.3%). At the time of presentation all patients were euthyroid. Following diagnosis of malignancy, a total thyroidectomy was performed in all patients, with the exception of 2, who had a thyroglossal duct cyst carcinoma of less than 10mm. Among the 10 patients who underwent total thyroidectomy, 7 (70%) patients had proven carcinoma in the thyroid gland, 3 with deposits of less than 10mm. The average size of the thyroid cancer deposits was 7.2mm (1–20mm). With a mean follow-up of is 44 months (5–120), all patients were alive and free of recurrence at the end of the study period. Conclusion: Thyroglossal duct cyst carcinoma is a rare condition and its management should be discussed in a multidisciplinary meeting. As with differentiated thyroid cancer originating in the thyroid gland, it bears extraordinary survival rates. Accordingly, the management of these cancers has shifted towards a more conservative approach although its peculiarities must be taken into account: ease of extracystic invasion and possible different lymph node invasion. (AU)

Objetivo: Revisar la presentación clínica, el diagnostico, la histología y las estrategias de tratamiento en una cohorte moderna de pacientes con carcinoma del conducto tirogloso. Diseño del estudio: Serie de casos retrospectiva utilizando PROCESS Guidelines. Localización: Unidad de cáncer de cabeza y cuello. Métodos: Los datos incluidos fueron: sexo, edad al diagnóstico, presentación clínica, función tiroidea, investigaciones diagnósticas, resultados citológicos, histología final, estadificación y estado durante el seguimiento. El riesgo de malignidad en el análisis citológico fue estratificado de acuerdo con la clasificación del Royal College of Pathologists del Reino Unido. Resultados: Se incluyeron 12 pacientes. La mayoría de ellos (66,7%) presentaron solamente un quiste del conducto tirogloso al diagnóstico. Solamente 4 pacientes tuvieron sospecha de malignidad de acuerdo con los resultados de la citología preoperatoria. En el momento de la presentación, todos los pacientes tenían función tiroidea normal. Después del diagnóstico, se realizó tiroidectomía total a todos los pacientes menos dos, que tuvieron carcinoma del conducto tirogloso menor de 10mm. Entre los 10 pacientes que recibieron tiroidectomía total, 7 (70%) sufrieron carcinoma en la glándula tiroides, 3 de ellos con depósitos menores de 10mm. El tamaño medio de los depósitos de carcinoma en la glándula tiroides fue de 7,2mm (1-20mm). Con una media de seguimiento de 44meses (5-120), todos los pacientes estaban vivos y libres de recidiva al final del periodo estudiado. Conclusión: El carcinoma del conducto tirogloso es una entidad poco frecuente y su manejo debe ser realizado por un equipo multidisciplinario. Igual que en el carcinoma diferenciado de tiroides que se origina en la glándula tiroides, las tasas de supervivencia son excelentes. ... (AU)