Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

Immunotherapy, cancer and PET. / Inmunoterapia, cáncer y PET.

The treatment of cancer by immunotherapy has been a revolution, as it is the first strategy that manages to control the disease for prolonged periods of time. Its efficacy is associated with different imaging response patterns and the appearance of new toxicities. We would highlight two patterns of tumour response: pseudoprogression, or growth of tumour lesions after the start of immunotherapy treatment, followed by a significant reduction in lesions, and hyperprogression, acceleration of tumour progression and metastasis early after the start of treatment. The emergence of such patterns has generated new metabolic response criteria, such as PECRIT, PERCIMT, imPERCIST and IPERCIST. Of particular interest are the new immunoPET-specific biomarkers, as they allow the identification of patients presenting the tumour target and are useful for predicting response to immunotherapy.

Pseudotumor fibroso inflamatorio pulmonar / No disponible

Los pseudotumores inflamatorios, también conocidos como granulomas de células plasmáticas, son una entidad de naturaleza inflamatoria y de causa desconocida, que pueden afectar a varios órganos, siendo la localización pulmonar infrecuente. Representan, según la literatura, el 0,7% de todas las tumoraciones pulmonares. Se considera un proceso benigno, que se caracteriza por un crecimiento anormal descontrolado de células inflamatorias cuya mejor opción terapéutica es la resección quirúrgica con buenos resultados, aunque se han descrito casos de recidiva a pesar de resección completa. Presentamos el caso de un paciente de 67 años con una masa pulmonar con diagnóstico definitivo de pseudotumor inflamatorio

Inflammatory pseudotumors, also known as plasmatic cell granulomas, are an inflammatory entity, of unknown origin, that can affect many organs, with an infrequent pulmonary localization, representing, 0,7% of all the lung tumors. It is considered to be a benign process, characterized by an abnormal and uncontrolled growth of inflammatory cells. The better therapeutic choice is surgical resection with good results, although it has been described recurrence despite complete resection. We present the case of a 67-year-old patient with a lung mass with definitive diagnosis of Inflammatory pseudotumor

Papel de los anticolinérgicos en la enfermedad asmática / No disponible

Los anticolinérgicos (AC) son escasamente utilizados en el asma a diferencia de lo que ocurre en la enfermedad pulmonar obstructiva crónica (EPOC) en la que está muy extendido su uso. Las directrices para el manejo del asma recomiendan el uso de AC únicamente durante las exacerbaciones, ya que los beneficios del uso de estos fármacos en la fase estable del asma aún no se han establecido. Estudios recientes han sugerido la implicación del sistema colinérgico en la fisiopatología y la patogenia del asma, al demostrar la capacidad de las células epiteliales bronquiales e inflamatorias para sintetizar y liberar acetilcolina (ACh) y para expresar receptores muscarínicos. La implicación de estos receptores en la modulación de determinados mecanismos inflamatorios en el asma y en los cambios estructurales que conducen al remodelado apoya este concepto. Estas consideraciones sugieren que los AC que actúan bloqueando determinados receptores muscarínicos constituirían una alternativa terapéutica en esta enfermedad. En este sentido, una serie de trabajos, recientemente publicados, han demostrado que los AC podrían ser eficaces en el tratamiento del asma estable (AU)

Anticholinergic agents are not usually chose for asthma treatment, compared with its widely use in Chronic Obstructive Pulmonary Disease. The asthma guidelines only recommend its use in acute asthma exacerbations, and has not been fully investigated its role in stable asthma. Recent studies have related the cholinergic system and asthma pathophysiology, as it has been observed the secretion of acetylcholine and the expression of muscarinic receptors by the airway ephitelium cells and inflammatory cells. These receptors play a regulatory role in inflammatory mechanisms and airway smooth muscle remodeling. These findings suggest that anticholinergics are an alternative therapeutic agent and probably are useful in stable asthma as adjuncts to other bronchodilator therapies (AU)

Infiltrados pulmonares bilaterales en paciente con inmunodeficiencia común variable / No disponible

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Absceso pulmonar con eosinofilia y aumento de IgE / No disponible

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Varón con síndrome constitucional y atelectasia completa del lóbulo superior derecho / No disponible

Presentamos el caso de un paciente varón de 62 años que ingresa procedente del Servicio de Urgencias por síndrome constitucional. El hallazgo en la radiografía simple de tórax de una atelectasia completa del lóbulo superior derecho, junto con el antecedente de tabaquismo del paciente no es sino una “pista que despista”. De este caso hemos aprendido que, por claros que parezcan los síntomas y signos, siempre debemos establecer un amplio diagnóstico diferencial, tanto para nosotros los clínicos como para el estudio anatomopatológico (AU)

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Preliminary results of the combination of bevacizumab and weekly Paclitaxel in advanced melanoma.

BACKGROUND: Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizumab, has demonstrated increased activity in combination with chemotherapy in many tumors. We intended to evaluate the activity of the combination of weekly paclitaxel and bevacizumab in previously treated metastatic melanoma. PATIENTS AND METHODS: Patients with previously treated metastatic melanoma received paclitaxel 70 mg/m(2) weekly and bevacizumab 10 mg/kg biweekly for 5 consecutive weeks every 6 weeks. RESULTS: Twelve patients were treated. Two patients (16.6%) achieved a partial response and 7 patients (58.3%) stable disease. Responses were seen in soft tissue, lung and brain metastases. Median disease-free and overall survival times were 3.7 and 7.8 months, respectively. Treatment was well tolerated. Main toxicities were grade 3 asymptomatic lymphopenia in 6 patients, grade 3 leucopenia in 2 patients, and grade 3 thrombocytopenia in 1 patient. CONCLUSIONS: Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.

[Small-cell lung cancer]. / Carcinoma microcítico de pulmón.

Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches.

Carcinoma microcítico de pulmón / No disponible

El cáncer microcítico de pulmón es uno de los tumores sólidos más agresivos, por su rápido crecimiento y por su tendencia a metastatizar desde fases tempranas. Sin embargo, también es uno de los tumores más sensibles a los tratamientos de quimioterapia y radioterapia, con los cuales algunos pacientes con enfermedad limitada pueden sobrevivir a largo plazo. Estas características han hecho de este tumor un modelo clínico sobre el cual se han probado múltiples estrategias de tratamiento, incluyendo tratamientos concomitantes con quimioterapia y radioterapia, esquemas de quimioterapia alternante o de altas dosis con soporte hematológico o la utilización de radioterapia holocraneal profi láctica. Además en los últimos años el cáncer microcítico de pulmón también se ha empleado como plataforma de desarrollo de tratamientos dirigidos contra dianas específi cas o de inmunoterapia

Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of wholebrain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches

[Mammographic findings in microcalcifications associated with breast cancer after neoadjuvant chemotherapy]. / Hallazgos mamográficos en las microcalcificaciones asociadas a cáncer de mama tras quimioterapia neoadyuvante.

OBJECTIVE: To evaluate the mammographic findings in microcalcifications associated with breast cancer after neoadjuvant chemotherapy. MATERIAL AND METHODS: From January 2000 to May 2005, a total of 99 breast cancer patients underwent neoadjuvant chemotherapy. Ten patients had microcalcifications on mammograms prior to treatment. We evaluated the evolution of the tumor and of the microcalcifications, correlating the imaging findings with the clinical and histological manifestations. RESULTS: Four different patterns of evolution were observed for the microcalcifications: the number of particles increased in two cases, remained stable in three, decreased in four, and in one patient the microcalcifications disappeared. The size of the tumor decreased in all cases. CONCLUSIONS: After neoadjuvant chemotherapy microcalcifications can evolve unpredictably and independently of tumor response.

Response of resistant melanoma to a combination of weekly paclitaxel and bevacizumab.

We report here a taxol-bevacizumab-responsive metastatic melanoma case. Although the patient had been heavily pretreated for two years, she did not show any stabilisation or objective response of her disease. After treatment with taxol and bevacizumab combination an impressive response was obtained.

Response of resistant melanoma to a combination of weekly paclitaxel and bevacizumab

We report here a taxol-bevacizumab-responsive metastatic melanoma case. Although the patient had been heavily pretreated for two years, she did not show any stabilisation or objective response of her disease. After treatment with taxol and bevacizumab combination an impressive response was obtained (AU)

Hallazgos mamográficos en las microcalcificaciones asociadas a cáncer de mama tras quimioterapia neoadyuvante / Mammographic findings in microcalcifications associated with breast cancer after neoadjuvant chemotherapy

Objetivo. Evaluar los hallazgos mamográficos en las microcalcificaciones asociadas al cáncer de mama tras el tratamiento con quimioterapia neoadyuvante (QTNA). Material y métodos. Desde enero de 2000 hasta mayo de 2005, un total de 99 pacientes con cáncer de mama se trataron con QTNA. De ellas, diez presentaban microcalcificaciones en las mamografías previas al tratamiento. Se estudió la evolución de la masa tumoral y de las microcalcificaciones, correlacionándola con las manifestaciones clínicas y anatomopatológicas. Resultados. Se observaron cuatro patrones en la evolución de las microcalcificaciones: el número de partículas aumentó en dos casos, permaneció estable en tres, disminuyó en cuatro y en uno las microcalcificaciones desaparecieron. La masa tumoral disminuyó en todos los casos. Conclusiones. Tras el tratamiento neoadyuvante las microcalcificaciones pueden evolucionar de manera impredecible e independiente de la respuesta tumoral

Objective. To evaluate the mammographic findings in microcalcifications associated with breast cancer after neoadjuvant chemotherapy. Material and methods. From January 2000 to May 2005, a total of 99 breast cancer patients underwent neoadjuvant chemotherapy. Ten patients had microcalcifications on mammograms prior to treatment. We evaluated the evolution of the tumor and of the microcalcifications, correlating the imaging findings with the clinical and histological manifestations. Results. Four different patterns of evolution were observed for the microcalcifications: the number of particles increased in two cases, remained stable in three, decreased in four, and in one patient the microcalcifications disappeared. The size of the tumor decreased in all cases. Conclusions. After neoadjuvant chemotherapy microcalcifications can evolve unpredictably and independently of tumor response

Tiotropio: un nuevo broncodilatador anticolinérgico para la EPOC

El uso del nuevo anticolinérgico tiotropio (Spiriva,Ba679 BR) puede suponer un avance en la terapia broncodilatadora de la enfermedad pulmonar obstructiva crónica (EPOC), lo que viene determinado por su especificidad de acción sobre los diferentes subtipos de receptores muscarínicos. Ello le confiere un efecto prolongado, y se puede utilizar una vez al día, lo que facilitará la adhesión y cumplimentación del plan terapéutico por parte del paciente. El tiotropio presenta una mayor potencia de acción que su predecesor, el bromuro de ipratropio (AU)

Recomendaciones para la organización y funcionamiento de las unidades especializadas en tabaquismo / Guidelines for organizing and operating specialized anti-smoking units

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Ecology of Indigenous Soil Rhizobia: Response of Bradyrhizobium japonicum to Readily Available Substrates.

Populations of indigenous Bradyrhizobium japonicum serocluster 123 and serogroups 110 and 138 were studied after various sugars were added to their soil habitat. Loam soil with approximately 10 cells of each group per g of soil were amended every 3 days with 0.1% glucose, sucrose, arabinose, xylose, or galactose. Enumerations of the populations were made every 12 days by immunofluorescence assay. Each B. japonicum population in the sugar-treated soils increased by about 1 log during the first 12 days, to a maximum of about 10 cells by day 36 or 48, irrespective of the sugar added. Maximum growth rates were similar for each group and occurred during the 12-day incubation period. The most rapid growth was in response to arabinose, with a mean generation time of about 3.0 days. Other mean doubling times were 4.0 days with glucose and galactose treatments, 4.5 days with xylose treatment, and 5.4 days with sucrose amendment. These data provide the first direct evidence that indigenous soil rhizobia can compete successfully with other soil bacteria for readily available substrates in soil in the absence of host legume roots or other rhizospheres. The growth rates in soil of the specific B. japonicum populations studied were nearly the same with a given sugar treatment but varied considerably with different sugars. The mean generation times of 3 to 5 days are among the first reported growth rates for heterotrophic bacteria in natural soil.