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

Altres ajuts: Acord transformatiu CRUE-CSICPurpose: 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

Análisis de la supervivencia competitiva en pacientes con carcinoma escamoso de cabeza y cuello

El paciente con carcinoma escamoso de cabeza y cuello cuenta con un riesgo importante de mortalidad competitiva derivado de los factores de riesgo (principalmente tabaco y alcohol) compartidos entre el tumor índice y la aparición de segundas neoplasias y enfermedades crónicas potencialmente letales. El análisis de la supervivencia mediante el método de riesgos competitivos permite el cálculo de la incidencia acumulada de múltiples eventos de desenlace simultáneamente, por lo que proporciona estimaciones de la probabilidad neta de mortalidad por distintas causas. Además, los pacientes que sobreviven cierto tiempo desde el diagnóstico del tumor precisan de un ajuste de la probabilidad de supervivencia, pues su pronóstico mejora transcurrido ese tiempo. Este ajuste es posible gracias al estudio de la supervivencia dinámica mediante el cálculo de la supervivencia condicional. En el presente estudio se realizó un análisis de la supervivencia competitiva en 4.823 pacientes de una base de datos oncológica del Hospital de Sant Pau con carcinoma escamoso de cabeza y cuello y con un seguimiento mínimo de un año. Se obtuvo una estimación de la incidencia acumulada de mortalidad relacionada con el tumor índice, con segundas neoplasias de cabeza y cuello, con segundas neoplasias no cabeza y cuello y no relacionada con el cáncer en función de las variables edad, sexo, estadio, Karnofsky, tratamiento, localización del tumor índice y consumo de tóxicos. El impacto de estas variables sobre los diferentes tipos de mortalidad se estudió mediante un análisis multivariante de Fine-Gray. De manera similar se estudió el impacto del estatus VPH sobre la mortalidad competitiva en pacientes con carcinoma de orofaringe. Adicionalmente se estimó la supervivencia condicional, global y específica, de los pacientes de la cohorte general. La mortalidad relacionada con el tumor siguió un patrón asintótico, con una incidencia acumulada a los 5 años del 30.6% y a los 25 años del 32.8%. La mortalidad relacionada con segundos cánceres de cabeza y cuello, con segundas neoplasias no cabeza y cuello, y no relacionada con el cáncer siguió un patrón lineal, incrementándose un 0.5% anual. Los resultados del estudio multivariante mostraron que la la mortalidad por el tumor índice se relacionó significativamente con todas las variables incluidas excepto el sexo y consumo de tóxicos. La mortalidad por segundo cánceres primarios de cabeza y cuello se relacionó con el estadio, localización del tumor índice, edad y consumo de tóxicos. La mortalidad por segundos cánceres primarios no cabeza y cuello se relacionó con la localización del tumor índice, edad, sexo y consumo de tóxicos. La mortalidad no relacionada con el cáncer se relacionó con todas las variables incluidas en el análisis excepto con el estadio. En pacientes con carcinoma de orofaringe se demostró una fuerte influencia del estatus VPH sobre la mortalidad relacionada con el tumor índice y con segundos cánceres primarios, pero no sobre la mortalidad no relacionada con el cáncer. El análisis de supervivencia condicional, global y específica, mostró una mejoría del pronóstico durante los 3 primeros años sobrevividos. El cáncer escamoso de cabeza y cuello es especialmente sensible al padecimiento de mortalidad por causas competitivas; en la presente serie casi la mitad de los fallecimientos fueron por causas no relacionadas con el tumor índice. El incremento de la supervivencia específica que proporcionan los nuevos tratamientos multimodales en el cáncer de cabeza y cuello, junto con el envejecimiento y subsecuente aumento de las morbilidades de la población, condicionan un escenario dónde el estudio de la mortalidad competitiva y condicional es cada vez más relevante.Head and neck cancer patients are at high risk of competing mortality because of shared risk factors (alcohol and tobacco) between the index tumor, second primary cancers and other comorbidities. Competing risks survival analysis allows simultaneous estimation of the cumulative incidence of different final events, providing net estimation of mortality by different causes. Patients that survive a number of years after tumor diagnosis experience an improvement in the chance of survival. Such an improvement may be estimated by dynamic survival study using conditional survival analysis. A competing survival analysis was performed on 4,283 patients with head and neck squamous cell carcinoma selected from a tertiary center oncologic database with a minimum follow-up of one year. Index tumor related mortality, second primary cancer mortality and non-cancer related mortality cumulative incidences were estimated depending on covariates sex, age, stage, Karnofsky, treatment modality, index tumor location and substance abuse. A Fine-Gray multivariate analysis was used to assess the impact of these covariates on each group of mortality. VPH status impact on competing survival on patients with oropharynx carcinomas was assessed as well. Finally, conditional global and specific survival on the whole cohort was estimated. Index tumor related mortality followed an asymptotic pattern, with a 5 and 25 year cumulative incidence of 30.6% and 32.8% respectively. Second primary head neck and non-head and neck cancer mortality and non-cancer related mortality followed a linear pattern, increasing 0.5% per year. Multivariate analysis showed that index tumor mortality was significantly related with all the covariates included except for sex and substance abuse. Second primary head and neck cancer mortality was related with stage, location, age and substance abuse. Second primary non-head and neck cancer mortality was related with index tumor location, age, stage and substance abuse. Non-cancer related mortality was related with all covariates included in the study except for the index tumor stage. A strong impact of VPH-status on index tumor related mortality and second cancer mortality was found in oropharynx carcinoma patients, but not for non-cancer related mortality. Conditional specific and global survival analysis showed an improvement on prognosis over the first 3 years after diagnosis. Head and neck cancer patients are at high risk for competing mortality; in this cohort almost half of the deaths were not related with the index tumor. Improvement in specific survival due to new multimodal treatments in head and neck cancer, as well as the increase in morbidity prevalence secondary to population ageing, is leading to a new scenario where competing and conditional mortality assessment is becoming much more relevant

Análisis de la supervivencia competitiva en pacientes con carcinoma escamoso de cabeza y cuello /

El paciente con carcinoma escamoso de cabeza y cuello cuenta con un riesgo importante de mortalidad competitiva derivado de los factores de riesgo (principalmente tabaco y alcohol) compartidos entre el tumor índice y la aparición de segundas neoplasias y enfermedades crónicas potencialmente letales. El análisis de la supervivencia mediante el método de riesgos competitivos permite el cálculo de la incidencia acumulada de múltiples eventos de desenlace simultáneamente, por lo que proporciona estimaciones de la probabilidad neta de mortalidad por distintas causas. Además, los pacientes que sobreviven cierto tiempo desde el diagnóstico del tumor precisan de un ajuste de la probabilidad de supervivencia, pues su pronóstico mejora transcurrido ese tiempo. Este ajuste es posible gracias al estudio de la supervivencia dinámica mediante el cálculo de la supervivencia condicional. En el presente estudio se realizó un análisis de la supervivencia competitiva en 4.823 pacientes de una base de datos oncológica del Hospital de Sant Pau con carcinoma escamoso de cabeza y cuello y con un seguimiento mínimo de un año. Se obtuvo una estimación de la incidencia acumulada de mortalidad relacionada con el tumor índice, con segundas neoplasias de cabeza y cuello, con segundas neoplasias no cabeza y cuello y no relacionada con el cáncer en función de las variables edad, sexo, estadio, Karnofsky, tratamiento, localización del tumor índice y consumo de tóxicos. El impacto de estas variables sobre los diferentes tipos de mortalidad se estudió mediante un análisis multivariante de Fine-Gray. De manera similar se estudió el impacto del estatus VPH sobre la mortalidad competitiva en pacientes con carcinoma de orofaringe. Adicionalmente se estimó la supervivencia condicional, global y específica, de los pacientes de la cohorte general. La mortalidad relacionada con el tumor siguió un patrón asintótico, con una incidencia acumulada a los 5 años del 30.6% y a los 25 años del 32.8%. La mortalidad relacionada con segundos cánceres de cabeza y cuello, con segundas neoplasias no cabeza y cuello, y no relacionada con el cáncer siguió un patrón lineal, incrementándose un 0.5% anual. Los resultados del estudio multivariante mostraron que la la mortalidad por el tumor índice se relacionó significativamente con todas las variables incluidas excepto el sexo y consumo de tóxicos. La mortalidad por segundo cánceres primarios de cabeza y cuello se relacionó con el estadio, localización del tumor índice, edad y consumo de tóxicos. La mortalidad por segundos cánceres primarios no cabeza y cuello se relacionó con la localización del tumor índice, edad, sexo y consumo de tóxicos. La mortalidad no relacionada con el cáncer se relacionó con todas las variables incluidas en el análisis excepto con el estadio. En pacientes con carcinoma de orofaringe se demostró una fuerte influencia del estatus VPH sobre la mortalidad relacionada con el tumor índice y con segundos cánceres primarios, pero no sobre la mortalidad no relacionada con el cáncer. El análisis de supervivencia condicional, global y específica, mostró una mejoría del pronóstico durante los 3 primeros años sobrevividos. El cáncer escamoso de cabeza y cuello es especialmente sensible al padecimiento de mortalidad por causas competitivas; en la presente serie casi la mitad de los fallecimientos fueron por causas no relacionadas con el tumor índice. El incremento de la supervivencia específica que proporcionan los nuevos tratamientos multimodales en el cáncer de cabeza y cuello, junto con el envejecimiento y subsecuente aumento de las morbilidades de la población, condicionan un escenario dónde el estudio de la mortalidad competitiva y condicional es cada vez más relevante.Head and neck cancer patients are at high risk of competing mortality because of shared risk factors (alcohol and tobacco) between the index tumor, second primary cancers and other comorbidities. Competing risks survival analysis allows simultaneous estimation of the cumulative incidence of different final events, providing net estimation of mortality by different causes. Patients that survive a number of years after tumor diagnosis experience an improvement in the chance of survival. Such an improvement may be estimated by dynamic survival study using conditional survival analysis. A competing survival analysis was performed on 4,283 patients with head and neck squamous cell carcinoma selected from a tertiary center oncologic database with a minimum follow-up of one year. Index tumor related mortality, second primary cancer mortality and non-cancer related mortality cumulative incidences were estimated depending on covariates sex, age, stage, Karnofsky, treatment modality, index tumor location and substance abuse. A Fine-Gray multivariate analysis was used to assess the impact of these covariates on each group of mortality. VPH status impact on competing survival on patients with oropharynx carcinomas was assessed as well. Finally, conditional global and specific survival on the whole cohort was estimated. Index tumor related mortality followed an asymptotic pattern, with a 5 and 25 year cumulative incidence of 30.6% and 32.8% respectively. Second primary head neck and non-head and neck cancer mortality and non-cancer related mortality followed a linear pattern, increasing 0.5% per year. Multivariate analysis showed that index tumor mortality was significantly related with all the covariates included except for sex and substance abuse. Second primary head and neck cancer mortality was related with stage, location, age and substance abuse. Second primary non-head and neck cancer mortality was related with index tumor location, age, stage and substance abuse. Non-cancer related mortality was related with all covariates included in the study except for the index tumor stage. A strong impact of VPH-status on index tumor related mortality and second cancer mortality was found in oropharynx carcinoma patients, but not for non-cancer related mortality. Conditional specific and global survival analysis showed an improvement on prognosis over the first 3 years after diagnosis. Head and neck cancer patients are at high risk for competing mortality; in this cohort almost half of the deaths were not related with the index tumor. Improvement in specific survival due to new multimodal treatments in head and neck cancer, as well as the increase in morbidity prevalence secondary to population ageing, is leading to a new scenario where competing and conditional mortality assessment is becoming much more relevant

Alteraciones del olfato en la COVID-19, revisión de la evidencia e implicaciones en el manejo de la pandèmia

Existe debate sobre si las alteraciones en el olfato deberían considerarse un síntoma de la COVID-19. Se realizó una revisión sistemática bibliográfica de los artículos indexados en PubMed sobre alteraciones del olfato en cuadros virales de vías respiratorias, con especial énfasis en la COVID-19. El objetivo principal fue encontrar evidencia de interés clínico que apoye la relación entre ansomia y COVID-19. Las alteraciones del olfato en procesos infecciosos de vías altas son frecuentes y en su mayoría responden a una causa obstructiva por edema de la mucosa nasal. Ocasionalmente aparece una disfunción olfatoria posviral de tipo neurosensorial, de pronóstico variable. La evidencia acerca de la anosmia en pacientes con COVID-19 es muy limitada, correspondiente a un grado 5 o D del Centre for Evidence-Based Medicine. De acuerdo con la evidencia disponible, parece razonable aplicar medidas de aislamiento, higiene y distanciamiento social a los pacientes con alteraciones del olfato de reciente aparición como único síntoma, aunque se debería estudiar la utilidad de la realización de pruebas diagnósticas a este tipo de sujetos

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

Assessing effectiveness of colonic and gynecological risk reducing surgery in Lynch Syndrome individuals

Background: Colorectal (CRC) and endometrial cancer (EC) are the most common types of cancer in Lynch syndrome (LS). Risk reducing surgeries (RRS) might impact cancer incidence and mortality. Our objectives were to evaluate cumulative incidences of CRC, gynecological cancer and all-cause mortality after RRS in LS individuals. Methods: Retrospective analysis of 976 LS carriers from a single-institution registry. Primary endpoints were cumulative incidence at 75 years of cancer (metachronous CRC in 425 individuals; EC and ovarian cancer (OC) in 531 individuals) and all-cause mortality cumulative incidence, comparing extended (ES) vs. segmental surgery (SS) in the CRC cohort and risk reducing gynecological surgery (RRGS) vs. surveillance in the gynecological cohort. Results: Cumulative incidence at 75 years of metachronous CRC was 12.5% vs. 44.7% (p = 0.04) and all-cause mortality cumulative incidence was 38.6% vs. 55.3% (p = 0.31), for ES and SS, respectively. Cumulative, incidence at 75 years was 11.2% vs. 46.3% for EC (p = 0.001) and 0% vs. 12.7% for OC (p N/A) and all-cause mortality cumulative incidence was 0% vs. 52.7% (p N/A), for RRGS vs. surveillance, respectively. Conclusions: RRS in LS reduces the incidence of metachronous CRC and gynecological neoplasms, also indicating a reduction in all-cause mortality cumulative incidence in females undergoing RRGS.This research has been funded by the Instituto de Salud Carlos III and co-funded by European Social Fund—ESF investing in your future—(grant CM19/00099), the Catalan-Balearic Society of Oncology (2018 grant of the Catalan-Balearic Society of Oncology), the Spanish Ministry of Economy and Competitiveness and co-funded by FEDER funds—A way to build Europe—(grant SAF2015-68016-R), CIBERONC and the Government of Catalonia (grants 2017SGR1282 and PERIS SLT002/16/0037). We thank the CERCA Program/Generalitat de Catalunya for institutional support

Podocytopathy in patients with monoclonal gammopathy: three patients and literature review

Background: renal manifestations of monoclonal gammopathies are of increasing interest among nephrologists. Typical manifestations include light chain cast nephropathy, amyloidosis or renal damage mediated by monoclonal immunoglobulin deposition. Podocytopathies in the setting of an underlying monoclonal gammopathy constitute a rare manifestation of these diseases and, although being described in the literature, remain a challenge since most data derive from case reports. Methods: a retrospective review of the clinical data of Hospital del Mar and Hospital Vall d'Hebron was performed to identify patients with minimal change disease (MCD) or focal and segmental glomerulosclerosis (FSGS) in the setting of neoplasms that produce monoclonal (M) protein. Additionally, a literature review on this topic was performed. This study aims to describe the clinical characteristics and outcomes of these patients. Results: three patients were identified to have podocytopathy and monoclonal gammopathy between the years 2013 and 2020. All three were males and >65 years of age. Two patients were diagnosed with MCD and one patient was diagnosed with FSGS. All patients underwent a kidney biopsy and light and electron microscopic studies were performed. The underlying causes of monoclonal gammopathy were multiple myeloma in two cases and Waldeström macroglobulinemia in one case. Two patients developed nephrotic syndrome during the follow-up. All patients were under active hematological treatment. One patient presented a complete remission of proteinuria whereas the other two presented a partial remission. Conclusions: podocytopathies may infrequently be found in patients with monoclonal gammopathies. Patients with overt glomerular proteinuria and hematological disorders with M protein should undergo a kidney biopsy for prompt diagnosis and to specify a prognosis. In addition, further study on this matter must be done to understand the pathophysiology and treat these patients appropriately

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona

Background: There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) and chemical elements (including some metals, essential trace elements, rare earth elements, and minority elements), are immunomodulatory and cause a range of adverse clinical events. There are no prospective studies on the effects of such substances on the incidence of SARS-CoV-2 infection and COVID-19. Objective: To investigate the influence of blood concentrations of POPs and elements measured several years before the pandemic on the development of SARS-CoV-2 infection and COVID-19 in individuals from the general population. Methods: We conducted a prospective cohort study in 154 individuals from the general population of Barcelona. POPs and elements were measured in blood samples collected in 2016-2017. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or by antibody serology using eighteen isotype-antigen combinations measured in blood samples collected in 2020-2021. We analyzed the associations between concentrations of the contaminants and SARS-CoV-2 infection and development of COVID-19, taking into account personal habits and living conditions during the pandemic. Results: Several historically prevalent POPs, as well as arsenic, cadmium, mercury, and zinc, were not associated with COVID-19, nor with SARS-CoV-2 infection. However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), and ruthenium (5.0 [1.8-14]) were associated with COVID-19, as were tantalum, benzo(b)fluoranthene, DDD, and manganese. Thallium (3.8 [1.6-8.9]), and ruthenium (2.9 [1.3-6.7]) were associated with SARS-CoV-2 infection, and so were lead, gold, and (protectively) iron and selenium. We identified mixtures of up to five substances from several chemical groups, with all substances independently associated to the outcomes. Conclusions: Our results provide the first prospective and population-based evidence of an association between individual concentrations of some contaminants and COVID-19 and SARS-CoV-2 infection. POPs and elements may contribute to explain the heterogeneity in the development of SARS-CoV-2 infection and COVID-19 in the general population. If the associations are confirmed as causal, means are available to mitigate the corresponding risks

p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis

Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior and patient outcome is primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show that sublethal doses of chemotherapy (CT) does not select previously resistant tumor populations but induces a quiescent state specifically to TP53 wildtype (WT) cancer cells, which is linked to the acquisition of a YAP1-dependent fetal phenotype. Cells displaying this phenotype exhibit high tumor-initiating and metastatic activity. Nuclear YAP1 and fetal traits are present in a proportion of tumors at diagnosis and predict poor prognosis in patients carrying TP53 WT CRC tumors. We provide data indicating the higher efficacy of CT together with YAP1 inhibitors for eradication of therapy resistant TP53 WT cancer cells. Together these results identify fetal conversion as a useful biomarker for patient prognosis and therapy prescription