Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma

Background Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. Methods We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan–Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). Results Median age was 58.9 years (range 42.8–81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0–1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2–3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1–38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9–7.3] and the median OS 10.1 months (95% CI 5.9–14.3). The objective response rate (ORR) was 44.4% (23.7–66.8%) and the disease control rate (DCR) 72.2% (49.4–88.5%) (AU)

Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma.

BACKGROUND: Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. METHODS: We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan-Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Median age was 58.9 years (range 42.8-81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2-3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1-38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9-7.3] and the median OS 10.1 months (95% CI 5.9-14.3). The objective response rate (ORR) was 44.4% (23.7-66.8%) and the disease control rate (DCR) 72.2% (49.4-88.5%). Efficacy tended to be greater in patients with the acquired T790M who had received osimertinib, with a median PFS of 6.3 (95% CI 2.1-10.5) versus (vs.) 4.8 (95% CI 3.5-6.1) and a median OS of 12.3 months (95% CI 8.6-16.0) vs. 6.7 months (95% CI 3.9-9.4), although this tendency was not statistically significant (p = 0.468 and p = 0.159, respectively). Sixteen patients (84.2%) had a total of 34 adverse events (AEs), with a median of two (0-6) AEs per patient. The most frequent AEs were asthenia (20.6%) and diarrhea (20.6%). One treatment-related death due to portal thrombosis was reported. CONCLUSIONS: Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.

Anatomic Segmentectomy in Nonintubated Video-Assisted Thoracoscopic Surgery.

Thoracic surgery has evolved into minimally invasive surgery, in terms of not only surgical approach but also less aggressive anesthesia protocols and lung-sparing resections. Nonintubated anatomic segmentectomies are challenging procedures but can be safely performed if some essentials are considered. Strict selection criteria, previous experience in minor procedures, multidisciplinary cooperation, and the 4 cornerstones (deep sedation, regional analgesia, oxygenation support and vagal blockade) should be followed. Better outcomes in postoperative recovery, including resumption of oral intake, chest tube duration, and hospital stay, and low complication and conversion rates, are encouraging but should be checked in larger multicenter prospective randomized trials.

Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

INTRODUCTION: Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

Sexualidad y drogas: aspectos medicolegales de interés para el médico general integral / Sexuality and drugs: Medical and legal aspects of interest for general doctors

Introducción: Los aspectos médicolegales en relación con la sexualidad y el uso indebido de drogas forman parte de los procedimientos médicolegales y constituyen elementos de especial interés para el trabajo del médico general integral. Objetivo: Motivar la reflexión acerca de los aspectos medicolegales en relación con la sexualidad y el uso de drogas, de interés para el Médico General Integral. Método: Se realizó una revisión comentada sobre las bases conceptuales relacionadas con la sexualidad y el uso indebido de drogas así como de las diferentes situaciones que se pueden presentar con esta asociación. Resultados: Se describen diferentes problemas médicos, sociales, jurídicos y éticos, asociados a la sexualidad y el uso de drogas que repercuten en el hombre como unidad bio-psico-socio-espiritual-cultural. Se explican los delitos que aparecen en el Código Penal cubano, relacionados con la sexualidad que son poco conocidos. Conclusiones: Los efectos dañinos de las drogas sobre la sexualidad, son descritos así como los diferentes tipos de delitos sexuales. Se describen especificidades que el médico debe conocer en relación con la asociación entre el consumo de alcohol y otras drogas, y los delitos sexuales. Se establecen los tipos de violación que pueden darse bajo el efecto de las drogas, así como los efectos propiciados por el efecto desinhibitorio que el alcohol provoca, tales como los embarazos inesperados y las infecciones de transmisión sexual, incluyendo el VIH/SIDA. Se recoge el protocolo de actuación para el examen de las presuntas víctimas de delitos sexuales.

Introduction: Several medical legal aspects associated to sexuality and the uses of drugs are part of the medical-legal procedure. It is very important for the Medicine Doctors work. Objective: To provoke the reflection about the problems associated to sexuality and the use of drugs in order to have Medicine Doctors be aware of some legal aspects of interest for their work. Methods: A comment revision about the conceptual basis of the sexuality and the use of drugs, and the several situations with this association was held. Results: Different medical, social, legal and ethical problems associated to sexuality and the use of drugs that have repercussion on man as a biological, social, spiritual and cultural unit, are presented in order to have Medicine Doctors be aware of some legal aspects of interest for their work. It has been made special emphasis in sexual crimes according to the Cuban penal code and how these crimes are defined and classified. Other less known crimes related to sexuality that appear in our penal code are also explained in detail. Conclusions: Are given about the destructive effect of drugs on man's sexuality and the different types of sexual crimes included in the Cuban penal code. The association between alcohol and drug consumption and sexual crimes, types of sexual abuses under drug effects and non-inhibited effects of alcohol propitiating undesired pregnancy and sexual infections including AIDS. The steps to follow according to medical practice during the physical exam of a presumed victim of sexual crime are also recommended in this paper.

Sexualidad y drogas: aspectos medicolegales de interés para el médico general integral / Sexuality and drugs: medical and legal aspects of interest for general doctors

Introducción: Los aspectos médicolegales en relación con la sexualidad y el uso indebido de drogas forman parte de los procedimientos médicolegales y constituyen elementos de especial interés para el trabajo del médico general integral. Objetivo: Motivar la reflexión acerca de los aspectos medicolegales en relación con la sexualidad y el uso de drogas, de interés para el Médico General Integral. Método: Se realizó una revisión comentada sobre las bases conceptuales relacionadas con la sexualidad y el uso indebido de drogas así como de las diferentes situaciones que se pueden presentar con esta asociación. Resultados: Se describen diferentes problemas médicos, sociales, jurídicos y éticos, asociados a la sexualidad y el uso de drogas que repercuten en el hombre como unidad bio-psico-socio-espiritual-cultural. Se explican los delitos que aparecen en el Código Penal cubano, relacionados con la sexualidad que son poco conocidos. Conclusiones: Los efectos dañinos de las drogas sobre la sexualidad, son descritos así como los diferentes tipos de delitos sexuales. Se describen especificidades que el médico debe conocer en relación con la asociación entre el consumo de alcohol y otras drogas, y los delitos sexuales. Se establecen los tipos de violación que pueden darse bajo el efecto de las drogas, así como los efectos propiciados por el efecto desinhibitorio que el alcohol provoca, tales como los embarazos inesperados y las infecciones de transmisión sexual, incluyendo el VIH/SIDA. Se recoge el protocolo de actuación para el examen de las presuntas víctimas de delitos sexuales(AU)

Introduction: Several medical legal aspects associated to sexuality and the uses of drugs are part of the medical-legal procedure. It is very important for the Medicine Doctors work. Objective: To provoke the reflection about the problems associated to sexuality and the use of drugs in order to have Medicine Doctors be aware of some legal aspects of interest for their work. Methods: A comment revision about the conceptual basis of the sexuality and the use of drugs, and the several situations with this association was held. Results: Different medical, social, legal and ethical problems associated to sexuality and the use of drugs that have repercussion on man as a biological, social, spiritual and cultural unit, are presented in order to have Medicine Doctors be aware of some legal aspects of interest for their work. It has been made special emphasis in sexual crimes according to the Cuban penal code and how these crimes are defined and classified. Other less known crimes related to sexuality that appear in our penal code are also explained in detail. Conclusions: Are given about the destructive effect of drugs on man's sexuality and the different types of sexual crimes included in the Cuban penal code. The association between alcohol and drug consumption and sexual crimes, types of sexual abuses under drug effects and non-inhibited effects of alcohol propitiating undesired pregnancy and sexual infections including AIDS. The steps to follow according to medical practice during the physical exam of a presumed victim of sexual crime are also recommended in this paper(AU)