Treatments for non-small cell lung cancer: a systematic quality assessment of clinical practice guidelines

Aim To evaluate the methodological quality of clinical practice guidelines (CPGs) on treatments for non-small cell lung cancer (NSCLC). Methods We searched MEDLINE, CPG developer websites, lung cancer societies, and oncology organizations to identify CPGs providing recommendations on treatments for NSCLC. The methodological quality for each CPG was determined independently by three appraisers using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument. Results Twenty-two CPGs met the eligibility criteria. The median scores per AGREE II domain were: scope and purpose 90.7% (64.8–100%), stakeholder involvement 76.9% (27.8–96.3%); rigor of development 80.9% (27.1–92.4%); clarity of presentation 89.8% (50–100%); applicability 46.5% (12.5–87.5%); and editorial independence 91.7% (27.8–100%). Most of the CPGs (54.5%) were rated as “recommended with modifications” for clinical use. Conclusions Overall, the methodological quality of CPGs proving recommendations on the management of NSCLC is moderate, but there is still room for improvement in their development and implementation (AU)

Treatments for non-small cell lung cancer: a systematic quality assessment of clinical practice guidelines.

AIM: To evaluate the methodological quality of clinical practice guidelines (CPGs) on treatments for non-small cell lung cancer (NSCLC). METHODS: We searched MEDLINE, CPG developer websites, lung cancer societies, and oncology organizations to identify CPGs providing recommendations on treatments for NSCLC. The methodological quality for each CPG was determined independently by three appraisers using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument. RESULTS: Twenty-two CPGs met the eligibility criteria. The median scores per AGREE II domain were: scope and purpose 90.7% (64.8-100%), stakeholder involvement 76.9% (27.8-96.3%); rigor of development 80.9% (27.1-92.4%); clarity of presentation 89.8% (50-100%); applicability 46.5% (12.5-87.5%); and editorial independence 91.7% (27.8-100%). Most of the CPGs (54.5%) were rated as "recommended with modifications" for clinical use. CONCLUSIONS: Overall, the methodological quality of CPGs proving recommendations on the management of NSCLC is moderate, but there is still room for improvement in their development and implementation.

Eficacia de la tomografía en el seguimiento del cáncer de pulmón tratado con inmunoterapia cubana

RESUMEN Introducción: el cáncer de pulmón representa en el mundo la primera causa de muerte oncológica. La tomografía computarizada es el medio diagnóstico más utilizado para clasificar esta enfermedad por estadios. Objetivo: determinar la eficacia de la tomografía computarizada en la evaluación de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana. Materiales y métodos: se realizó un estudio de evaluación, longitudinal, retrospectivo, analítico, en pacientes con cáncer de pulmón de células no pequeñas en estadio avanzado, tratados con inmunoterapia activa cubana, después de la primera línea de tratamiento con quimioterapia o quimiorradioterapia, entre el 1 de enero de 2013 y el 31 de diciembre de 2017. El universo lo constituyeron 91 pacientes tratados con Racotumomab y CIMAvax-EGF. Los datos se obtuvieron de las historias clínicas individuales, se incorporaron en una base de datos en Excel y se analizaron estadísticamente con el paquete SPSS 23. Resultados: del total de pacientes, 28 recibieron la vacuna Racotumomab y 63 la CIMAvax-EGF: pseudoprogresó el 12,5 % de los tratados con Racotumomab y el 28 % de los que lo fueron con CIMAvax-EGF. Se observó que la mayor supervivencia fue en los pseudoprogresores. Conclusiones: es eficaz el estudio tomográfico en la evaluación de respuesta de la pseudoprogresión de la enfermedad en pacientes con cáncer de pulmón de células no pequeñas, tratados con inmunoterapia cubana.

ABSTRACT Introduction: lung cancer represents the first cause of oncological death in the world. Computed tomography is the most used diagnostic mean to classify the disease by stages. Objective: to determine the efficacy of computed tomography in the evaluation of the disease pseudo-progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy. Materials and methods: a longitudinal, retrospective, analytical study was conducted in patients with non-small cells lung cancer in advanced stage, treated with Cuban active immunotherapy after the first line of treatment with chemotherapy and chemoradiotherapy, between January 1, 2013 and December 31, 2017. The universe were 91 patients treated with Racotumomab and CIMAvax-EGF. Data were collected from personal clinical records, incorporated in an Excel database and statistically analyzed with the SPSS 23 package. Results: 28 patients from the total received the Racotumomab vaccine and 63 received the CIMAvax-ECG vaccine. 12.5 % of those treated with Racotumomab and 28 % of those treated with CIMAvax-ECG pseudo progressed. The greatest survival was found in pseudo progressors. Conclusions: the computed tomographic studio is efficacious in evaluating the response of the disease pseudo progression in patients with non-small cells lung cancer, treated with Cuban immunotherapy.

Estadificación nodular linfática y supervivencia en pacientes operados por carcinoma pulmonar no microcítico / Lymphatic nodular staging and survival in patients operated due to non-small cell lung cancer

Introducción: En los pacientes con cáncer de pulmón resulta vital el tratamiento quirúrgico, pues posibilita una estadificación patológica minuciosa, así como un pronóstico y tratamiento acordes con la carga tumoral de cada paciente. Objetivo: Determinar la influencia del tipo de linfadenectomía mediastinal en la supervivencia de pacientes operados por cáncer pulmonar de células no pequeñas. Métodos: Se realizó un estudio descriptivo y longitudinal en el Servicio de Cirugía General del Hospital Provincial Clínico-Quirúrgico Docente Saturnino Lora de Santiago de Cuba, durante un período de 10 años (de 2009 a 2019), en 55 pacientes seleccionados aleatoriamente, quienes recibieron algún tipo de linfadenectomía del mediastino además de resección pulmonar. En el procesamiento estadístico, se utilizaron el número absoluto, el porcentaje y la media como medidas de resumen; también la prueba de independencia de la Χ2, para identificar la posible asociación entre variables, y el método de Kaplan-Meier, para precisar la supervivencia. Resultados: La técnica de linfadenectomía mediastínica más utilizada fue el muestreo ganglionar (47,3 %), con la cual también se obtuvo un mayor porcentaje (84,6) de resultados negativos en cuanto a invasión neoplásica, a diferencia de lo observado con la disección ganglionar sistemática, que reveló positividad de infiltración tumoral en un elevado número de pacientes (52,9 %). Asimismo, los pacientes operados mediante disección ganglionar sistemática mostraron mejor supervivencia a los 6 meses (100 %) y al año (87,5 %); a los 5 años las cifras de supervivencia con esta técnica fueron superiores a las obtenidas con todos los tipos de escisiones ganglionares practicadas. Conclusiones: Existió mayor probabilidad del diagnóstico de invasión linfática del mediastino y una mejor supervivencia en los pacientes tratados con disección ganglionar sistemática. Por ello, se recomienda protocolizar dicho tratamiento quirúrgico, lo cual pudiera estar avalado por un ensayo clínico que permita comparar grupos homogéneos que reciban cada tipo de linfadenectomía, respectivamente, a fin de recoger una evidencia científica relevante y concluyente.

Introduction: In the patients with lung cancer it is vital the surgical treatment, because it facilitates a meticulous pathological staging, as well as a prognosis and treatment according to each patient tumoral charge. Objective: To determine the influence of the mediastinal limphadenectomy type in the survival of patients operated due to non-small cells lung cancer. Methods: A descriptive and longitudinal study was carried out in the General Surgery Service of Saturnino Lora Teaching Clinical-Surgical Provincial Hospital in Santiago de Cuba, during 10 years (from 2009 to 2019), in 55 patients selected at random who received some type of mediastinum lymphadenectomy besides lung resection. In the statistical processing, the absolute number, percentage and the mean were used, as summary measures; also the chi-squared test to identify the possible association among variables, and the Kaplan-Meier method, to specify survival. Results: The most used medistinic lymphadenectomy technique was the ganglionar sampling (47.3 %), with which a higher percentage of negative results was also obtained (84.6) as regards neoplastic invasion, contrary to that is observed with the systematic ganglionar dissection that revealed metastasis positivity in a high number of the patients that received it (52.9 %). Likewise, patients operated by means of systematic ganglionar dissection showed a better survival 6 months later (100 %) and a year later (87.5 %); after 5 years the survival number with this technique was superior to all the types of ganglionar excisions practiced. Conclusions: There was a higher probability of the mediastinic lymphatic infiltration diagnosis and better survival in the patients treated with systematic ganglionar dissection. Reason why, it is recommended to protocolize this surgical treatment, which could be endorsed by a clinical trial that allows to compare homogeneous groups that receive each type of lymphadenectomy, respectively, in order to obtain an outstanding and conclusive scientific evidence.

Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study.

BACKGROUND: The objective of this study was to investigate the association between the onset of TD and treatment efficacy in NSCLC patients who initiated anti-PD-1 blockade (Nivolumab®) and to assess the impact of TD severity and subtype on nivolumab efficacy. MATERIALS AND METHODS: This study was performed at a referral oncology center between July 20, 2015 and June 30, 2018. Patients with histologically confirmed stage IIIB/IV NSCLC in progression after one or two lines of treatment and who initiated Nivolumab were included. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to TD status [TD(+) versus TD(-)], severity [moderate thyroid dysfunction: TSH level between 0.1 and 0.4 or 4.0 and 10 mIU/L and severe thyroid dysfunction: TSH ≤ 0.1 or ≥ 10mUI/L) and subtype (isolated hypothyroidism, isolated hyperthyroidism and hyperthyroidism then hypothyroidism)]. Clinical endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 194 eligible patients, 134 patients (median age, 63 yo; 70.1% male) were included. Forty (29.9%) patients were classified in TD(+) and had a longer OS of 29.8 months (95% CI 18.8-NR) versus 8.1 months (95% CI 5.5-11.5) in TD(-) group (p < 0.001). PFS was also longer (8.7 months (95% CI 5.3-15.1) in TD(+) versus 1.7 months (95% CI 1.6-1.9) in TD(-) group (p < 0.001). In Cox proportional hazards analysis, TD remained an independent predictive factor of OS/PFS. Severity and subtype of TD were not correlated with OS/PFS. CONCLUSIONS: This study suggested that TD induced by Nivolumab appears to be an independent predictive factor of survival, irrespective of TD severity and subtype.

Vacuna terapéutica racotumomab en un anciano con cáncer avanzado de pulmón / Racotumomab therapeutic vaccine in an elderly with advanced lung cancer

Se presenta el caso clínico de un anciano de 84 años de edad, fumador, con diagnóstico de cáncer de pulmón en etapa IV, quien fue incluido en el ensayo clínico de fase III para ser tratado con racotumumab. Se observó mejoría clínica y del estado general del paciente, pues según la escala funcional concluyó el estudio con ECOG 0. Por tanto, es oportuno destacar que esta vacuna incrementa la supervivencia de los afectados por cáncer de pulmón de células no pequeñas recurrentes o en estadios avanzados.

The case report of a 84 years elderly smoker, is presented with diagnosis of lung cancer in stage IV who was included in the phase III clinical trial to be treated with racotumomab. Clinical improvement and recovery of the patient's general state was observed, because according to the functional scale the study concluded with ECOG 0. Therefore, it is opportune to highlight that this vaccine increases the survival of those affected by recurrent non-small cells lung cancer or in advanced stages.

Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC.

Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene addicted tumor. In these patients, despite the clear benefits of tyrosine kinase inhibitors therapy, the development of acquired resistance and progressive disease is inevitable in most cases and liquid biopsy is important for molecular characterization at resistance and, being non-invasive, may be useful for disease monitoring. In this review, the authors will focus on the applications of liquid biopsy in EGFR-mutated non small cells lung cancer at diagnosis, during treatment and at progression, describing available data and possible future scenarios.

Uso de la vacuna CIMAvax-EGF® como práctica médica habitual / Use of the vaccine CIMAvax-EGF® as habitual medical practice

Se realizó un estudio descriptivo y longitudinal de 58 pacientes con cáncer de pulmón de células no pequeñas, atendidos en la consulta de Sombras Pulmonares correspondiente al Servicio de Neumología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero del 2013 hasta igual mes del 2018, quienes eran tratados con CIMAvax-EGF® como práctica médica habitual, con vistas a determinar las características clinicoepidemiológicas de estos. En la serie primaron el sexo masculino y las edades de 60 a 79 años; asimismo, resultaron más frecuentes la etapa IV de la enfermedad y el adenocarcinoma como variedad histológica. Con el uso de la vacuna la mayoría de los pacientes presentaron una supervivencia de 12,9 meses y una respuesta terapéutica de enfermedad no progresora

A descriptive and longitudinal study of 58 patients with lung cancer of non small cells, assisted in the service of Lung Shades corresponding to the Pneumology Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital was carried out in Santiago de Cuba, from January, 2013 to the same month of 2018, who were treated with CIMAvax-EGF® as habitual medical practice, with the aim of determining the clinical and epidemiological characteristics of them. The male sex and ages from 60 to 79 years prevailed in the series; also, stage IV of the disease and the adenocarcinoma as histological variety were more frequent. With the use of the vaccine most of the patients presented a survival of 12.9 months and a therapeutic response of the non progressive disease

MiR-410 induces stemness by inhibiting Gsk3ß but upregulating ß-catenin in non-small cells lung cancer.

Our previous research indicated miR-410 played a critical role in promoting the tumorigenesis and development of NSCLC (non-small cells lung cancer). MiR-410 has been recently reported to be crucial for development and differentiation of embryonic stem cells. But it remains elusive whether miR-410 stimulates the stemness of cancer until now. Herein, we identify miR-410 induces the stemness and is associated with the progression of NSCLC. We demonstrate miR-410 increases the levels of stem cells marker Sox2, Oct4, Nanog, CXCR4 as well as lung cancer stem cells surface marker CD44 and CD166. MiR-410 promotes stem cells-like properties such as proliferation, sphere formation, metastasis and chemoresistance. Moreover, Gsk3ß is directly targeted and post-transcriptionally downregulated by miR-410. Also, the expression levels of miR-410 and Gsk3ß may be correlated to clinicopathological differentiation in NSCLC tumor specimens. Additionally, we demonstrate miR-410 induces stemness through inhibiting Gsk3ß but increasing Sox2, Oct4, Nanog and CXCR4, which binds to ß-catenin signaling. In conclusion, our findings identify the miR-410/Gsk3ß/ß-catenin signaling axis is a novel molecular circuit in inducing stemness of NSCLC.