Importancia de la imagen en la valoración de la respuesta al tratamiento con inmunoterapia del cáncer de pulmón / The Importance of Imaging Studies in the Assessment of Response to Immunotherapy in Lung Cancer

En los últimos años la inmunoterapia (particularmente los inhibidores de los puntos de control inmunitario) ha suscitado un gran interés en el tratamiento de los pacientes con cáncer de pulmón, revolucionando el manejo de los pacientes con tumores localmente avanzados/metastásicos y generando esperanzas entre los pacientes y los médicos que diagnostican y tratan a estos enfermos. Estos fármacos se han convertido (combinados o no con otras terapias) en el tratamiento estándar de muchos pacientes con cáncer de pulmón y se espera que su uso aumente significativamente en un futuro próximo. En este manuscrito revisaremos la importancia creciente de las técnicas de imagen en la valoración de respuesta al tratamiento con inmunoterapia de los pacientes con cáncer de pulmón, haciendo hincapié en los nuevos criterios radiológicos específicos de respuesta con inmunoterapia, en las respuestas radiológicas atípicas (seudoprogresión, respuestas disociadas, hiperprogresión) y en las principales manifestaciones radiológicas de los eventos adversos asociados a la inmunoterapia (reacciones sarcoideas, toxicidades pulmonares, etc.). Los neumólogos deben conocer no solo las respuestas radiológicas atípicas de la inmunoterapia y sus implicaciones pronósticas, sino también sus efectos secundarios y los nuevos criterios radiológicos de respuesta desarrollados para valorar la respuesta al tratamiento. En este trabajo se tratarán conceptos claves como «seudoprogresión», «respuesta paradójica», «hiperprogresión» o «progresión no confirmada» y su significado en el manejo de los pacientes con cáncer de pulmón tratados con inmunoterapia

Immunotherapy (particularly immune checkpoint inhibitors) in the treatment of patients with lung cancer has aroused great interest in recent years, revolutionized the management of patients with locally advanced/metastatic disease, and given hope to both patients and treating physicians. These drugs, in combination or in monotherapy, have become the standard treatment for many patients with lung cancer, and their use is expected to increase significantly in the near future. In this article, we will review the growing importance of imaging techniques in the evaluation of therapeutic response to immunotherapy in lung cancer patients, with emphasis on the new specific radiological criteria on response to immunotherapy, atypical radiological responses (pseudoprogresion, dissociative responses, hyperprogresion), and the main radiological manifestations of adverse events associated with immunotherapy (sarcoid reactions, pulmonary toxicities, etc.). Pulmonologists must be familiar not only with atypical radiological responses to immunotherapy and their prognostic implications, but also with their effects and the new radiological criteria of response to assess treatment response. In this study, we will address key concepts such as "pseudoprogresion", "paradoxical response", "hyperprogresion", or "unconfirmed progression", and their significance in the management of patients with lung cancer treated with immunotherapy

The Importance of Imaging Studies in the Assessment of Response to Immunotherapy in Lung Cancer. / Importancia de la imagen en la valoración de la respuesta al tratamiento con inmunoterapia del cáncer de pulmón.

Immunotherapy (particularly immune checkpoint inhibitors) in the treatment of patients with lung cancer has aroused great interest in recent years, revolutionized the management of patients with locally advanced/metastatic disease, and given hope to both patients and treating physicians. These drugs, in combination or in monotherapy, have become the standard treatment for many patients with lung cancer, and their use is expected to increase significantly in the near future. In this article, we will review the growing importance of imaging techniques in the evaluation of therapeutic response to immunotherapy in lung cancer patients, with emphasis on the new specific radiological criteria on response to immunotherapy, atypical radiological responses (pseudoprogresion, dissociative responses, hyperprogresion), and the main radiological manifestations of adverse events associated with immunotherapy (sarcoid reactions, pulmonary toxicities, etc.). Pulmonologists must be familiar not only with atypical radiological responses to immunotherapy and their prognostic implications, but also with their effects and the new radiological criteria of response to assess treatment response. In this study, we will address key concepts such as "pseudoprogresion", "paradoxical response", "hyperprogresion", or "unconfirmed progression", and their significance in the management of patients with lung cancer treated with immunotherapy.

Development of Thyroid Carcinoma During Treatment With Pembrolizumab in a Lung Cancer Patient.

Pembrolizumab, a programmed death 1 inhibitor, has been shown to have clinically significant efficacy in different types of cancer, providing long-term survival benefit for patients with lung cancer. Herein, we report the development of a primary thyroid cancer in a lung cancer patient that was being treated with pembrolizumab. Primary thyroid malignancy (and not only metastatic disease or immunotherapy-induced thyroiditis) should be considered in patients with lung cancer being treated with immune checkpoint inhibitors who develop new incidental thyroid lesions on imaging studies.

Efficacy of immunotherapy in sarcomatoid lung cancer, a case report and literature review.

Sarcomatoid carcinoma is a subtype of non-small cell lung cancer (NSCLC) characterized by mesenchymal - epithelial transition component and awful prognosis. In this report, based on a case of stage IV lung sarcomatoid carcinoma with an extraordinary evolution and survival over 4 years, we address unresolved questions about the treatment of this cancer. We also make a literature review about the key factors that characterize this histology and that should be considered when treating those patients. Sarcomatoid carcinoma presents with mutations as KRAS, EGFR, ALK or MET in up to 70% of cases, and an important expression of PD-L1 (also called B7-H1), which can influence treatment of those patients with new drugs as immune checkpoint inhibitors. Immunotherapy has changed the horizon of patients with stage IV lung cancers without driver mutations, as their survival has improved extraordinary. Moreover, radical treatments are being considered in long survivors with oligometastatic disease. In this report, we review targeted and radical therapy, treatment duration and the mechanisms responsible of disease evolution of sarcomatoid tumors.

Retos de la troncalidad y su aplicación en el entorno hospitalario / Challenges of the core subjects and their application in the hospital environment

El sistema de formación sanitaria especializada en España dio comienzo oficialmente en el año 1978 con la publicación del RD 2015/1978, aunque, ya antes, hospitales pioneros habían desarrollado programas de formación para médicos internos y residentes. Desde entonces, y desde la entrada en vigor de la Ley 44/2003, de 21 de noviembre, de Ordenación de las Profesiones Sanitarias (LOPS) y sus normas de desarrollo, se han producido muchos avances; si bien, por incidir directamente en desarrollo del proceso de formación sanitaria especializada, pocos han sido tan trascendentes como los derivados de la aplicación de los preceptos recogidos en el RD 639/2014, de 28 de julio, por el que se regula, entre otros aspectos de la formación sanitaria especializada, la troncalidad. Además de la definición de una nueva organización de las especialidades, que agrupa la mayoría de ellas (39 de las 56 existentes) en torno a 5 troncos, uno de los aspectos más novedosos es la incorporación de instrumentos de evaluación, que permitirán medir la adquisición de las competencias incluidas en cada programa formativo. Esto va a requerir un esfuerzo adicional por parte de todos, principalmente tutores y comisiones de docencia, pero sin duda contribuirá a sistematizar y normalizar la supervisión de la formación de todos los residentes, a la par que nos permitirá tener un elemento más para evaluar la calidad de la formación. Además de los tutores y las comisiones de docencia, las comisiones nacionales de especialidad y el Consejo Nacional de Especialidades en Ciencias de Salud, también están llamados a tener un papel muy importante, puesto que en ellos recae el desarrollo, implantación y seguimiento de la troncalidad, velando, entre otras cosas, por la calidad de la formación, al ser responsables de la elaboración de los programas formativos, y por el cumplimiento de los objetivos generales del proceso. Sin duda, la puesta en marcha de este RD 639/2014 nos plantea grandes retos, pero también nos brinda una oportunidad para reflexionar conjuntamente sobre las fortalezas y debilidades de la actual formación sanitaria especializada, para así contribuir a mejorarla, implementando un nuevo modelo que contribuya a fortalecer nuestro sistema sanitario

The Specialized Healthcare Training system through residency (SHT) was first regulated in Spain in 1978 when the Royal Decree (RD) 2015/1978 was published, although prior to that, pioneering hospitals had developed training programs for medical interns and residents. Since then there have been many advances including the far-reaching publication in 2014 of RD 639/2014 which regulates, among other things, the core curricula specialties (named "troncalidades") - the re-specialization of the areas of special training. The implementation of the "troncalidad" project faces several challenges, which are anticipated to stem from the modification of current training structures, the definition of competencies, the accreditation process, evaluation and feedback. The article discusses the vision of the Standing Commission, its current status and the challenges of the implementation of a new model that will strengthen our health care system

Sumario ejecutivo de las recomendaciones SEPAR de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas / Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer

La Sociedad Española de Neumología y Cirugía Torácica (SEPAR), a través de las áreas de Cirugía Torácica y de Oncología Torácica, ha promovido la realización de un manual de recomendaciones para el diagnóstico y el tratamiento del cáncer de pulmón de células no pequeñas. Las elevadas incidencia y mortalidad de esta patología hacen necesaria una constante actualización de las mejores evidencias científicas para su consulta por parte de los profesionales de la salud. Para su confección se ha contado con un amplio grupo de profesionales de distintas especialidades que han elaborado una revisión integral, que se ha concretado en 4 apartados principales. En el primero se ha estudiado la prevención y el cribado de la enfermedad, incluyendo los factores de riesgo, el papel de la deshabituación tabáquica y el diagnóstico precoz mediante programas de cribado. En un segundo apartado se ha analizado la presentación clínica, los estudios de imagen y el riesgo quirúrgico, incluyendo el cardiológico y la evaluación funcional respiratoria. Un tercero trata sobre los estudios de confirmación cito-histológica y de estadificación, con un análisis de las clasificaciones TNM e histológica, métodos no invasivos y mínimamente invasivos, así como las técnicas quirúrgicas para el diagnóstico y estadificación. En un cuarto y último capítulo se han abordado aspectos del tratamiento, como el papel de las técnicas quirúrgicas, la quimioterapia, la radioterapia, el abordaje multidisciplinar por estadios y otros tratamientos dirigidos frente a dianas específicas, terminando con recomendaciones acerca del seguimiento del cáncer de pulmón y los tratamientos paliativos quirúrgicos y endoscópicos en estadios avanzados

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages

Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer. / Sumario ejecutivo de las recomendaciones SEPAR de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals. To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages.

Recomendaciones SEPAR de diagnostico y tratamiento del cancer de pulmón de celulas no pequeñas / Recommendations of the Spanish Society of Pneumology and Thoracic Surgery on the diagnosis and treatment of non-small-cell lung cancer

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Career opportunities and benefits for young oncologists in the European Society for Medical Oncology (ESMO).

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly supervised by the ESMO Executive Board and the ESMO President. It offers unique resources for YOs at all stages of training and includes a broad variety of fellowship opportunities, educational courses, scientific meetings, publications and resources. In this article, we provide an overview of the activities and career development opportunities provided by ESMO to the next generation of oncologists.

Multidisciplinary approach in stage III non-small-cell lung cancer: standard of care and open questions.

Lung cancer is the most frequent cause of cancer death worldwide and its global incidence has been steadily increasing during recent decades. A third of patients with newly diagnosed non-small-cell lung cancer (NSCLC) present with locally advanced disease. There is not a single widely accepted standard of care for these patients because of the wide spectrum of presentation of the disease. Although feasible and safe in experienced hands, evidence that surgical resection after induction treatment improves overall survival (OS) is lacking. For resectable or potentially resectable stage III, the findings of two phase III trials suggest that surgical resection should not be considered a standard of care but rather reserved for selected patients after critical multidisciplinary assessment, in whom surgery improves survival after downstaging if pneumonectomy can be avoided or in some T4N0-1 resectable tumours. For unresectable stage III NSCLC the standard of care is a combination of chemotherapy and radiotherapy. In those patients with good performance status and minimal weight loss, the concurrent approach has resulted in a statistically significant improvement in OS rates compared with a sequential approach in randomised clinical trials, although several questions remain unresolved.

SEOM clinical guidelines for the treatment of non-small-cell lung cancer: an updated edition.

The purpose of this article is to provide updated recommendations for the diagnosis and treatment of patients non-small-cell lung cancer (NSCLC). The staging system for lung cancer has recently been revised by the International Association for Study of Lung Cancer and patients with NSCLC shall now be staged according to the UICC system 7th edition. Recommendations for treatment were based on treatment strategies that improve overall survival. In functionally fit patients with stage I-II disease surgical resection is recommended. Four cycles of adjuvant cisplatin-based chemotherapy is recommended in patients with pathologic stage II-III. For patients with stage IIIA and non-bulky mediastinal lymph node survival was significantly improved with induction chemotherapy plus surgical resection. Patients with unresectable or bulky stage IIIA and those with stage IIIB, should be treated with platinum-based chemotherapy and thoracic radiotherapy. For patients with metastatic disease and performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For elderly patients and those with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with platinum-based chemotherapy, except for patients with certain clinical characteristics. Maintenance therapy with pemetrexed or erlotinib increases survival in patients who did not progress after 4 cycles of a platinum based chemotherapy. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs.

[Secondary hypopituitarism due to hypothalamic metastasis from small cell lung cancer]. / Hipopituitarismo secundario debido a metástasis en región hipotalámica de carcinoma microcítico de pulmón.

Parasellar and hypothalamic metastases are uncommon. Their principal clinical manifestation is diabetes insipidus. Associated hypopituitarism is very rare. We report the case of a 54-year-old man with small cell lung cancer and hypopituitarism. A brain magnetic resonance imaging scan revealed a mass in the anterior region of the third ventricle with no clear etiology. The patient began chemotherapy treatment and the mass disappeared, which confirmed the diagnosis of secondary hypopituitarism caused by hypothalamic metastasis from small cell lung cancer.

Hipopituitarismo secundario debido a metástasis en región hipotalámica de carcinoma microcítico de pulmón / Secondary hypopituitarism caused by hypothalamic metastasis from small cell lung cancer

Las metástasis en la región selar e hipotalámica son raras y la principal manifestación clínica es la diabetes insípida. Un hipopituitarismo concomitante se produce en muy pocas ocasiones. Presentamos el caso de un varón de 54 años con carcinoma microcítico de pulmón e hipopituitarismo. Una resonancia magnética cerebral reveló una lesión en la cara anterior del tercer ventrículo sin etiología clara. El paciente inició tratamiento con quimioterapia y la lesión desapareció. Por lo tanto, el paciente fue diagnosticado de hipopitituarismo secundario a metástasis hipotalámica de carcinoma microcítico de pulmón (AU)

Parasellar and hypothalamic metastases are uncommon. Their principal clinical manifestation is diabetes insipidus. Associated hypopituitarism is very rare. We report the case of a 54-year-old man with small cell lung cancer and hypopituitarism. A brain magnetic resonance imaging scan revealed a mass in the anterior region of the third ventricle with no clear etiology. The patient began chemotherapy treatment and the mass disappeared, which confirmed the diagnosis of secondary hypopituitarism caused by hypothalamic metastasis from small cell lung cancer (AU)

[Treatment of acneiform rash by epidermal growth factor inhibitors with oral tetracyclines]. / Tratamiento de la erupción acneiforme por inhibidores del factor de crecimiento epidérmico con tetraciclinas orales.

INTRODUCTION: Epidermal growth factor inhibitors (EGFR) are new antineoplastic agents that are increasingly being developed. They are basically used as second line treatment in advanced stage tumors. Appearance of a facial acneiform rash in patients treated with these drugs is common and characteristic. The literature proposes multiple topical and systemic treatment options. Up to now, there is no clear evidence on any of them. PATIENTS AND METHODS: A descriptive study of 6 patients who were treated with 100 mg daily dose of doxycycline for 3 weeks was conducted. Clinical characteristics of the patients and treatment efficacy were analyzed. RESULTS: Five of the six patients achieved total resolution of the acneiform rash with this treatment. One patient achieved partial response. After long follow-up periods and in spite of following treatment with the EGFR inhibitors, no relapse was observed. CONCLUSIONS: Doxycycline is suggested as an effective treatment in this disease. Even though it is a short series, the results in our patients support this efficacy.