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Background: The present article describes three cases of patients in cardiogenic shock (CS) with previous cardiac surgery that made them initially inoperable. Perioperative support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) improved haemodynamic status and results in these high-risk patients. Case summary: Case 1 is a 57-year-old male morbidly obese with previous aortic valve replacement (AVR) who presented with chest pain and developed cardiac arrest. Cardiopulmonary resuscitation and femoral VA-ECMO were initiated. Three days later, a redo AVR was performed. Veno-arterial extracorporeal membrane oxygenation was maintained for 12 days, followed by 7 days of veno-venous ECMO for complete recovery. Case 2 features a 39-year-old male with two previous mitral valve replacements (MVRs). The first is due to papillary muscle rupture, and the second is due to endocarditis of the mitral prosthesis. He presented with CS and pulmonary oedema. Emergency surgery was performed and the patient was then placed in VA-ECMO. Weaning off was achieved 3 days after surgery. Case 3 is a 21-year-old female with a previous MVR due to rheumatic disease. She presented with CS, severe mitral prosthesis stenosis, and a pulmonary embolism. Femoral VA-ECMO was initiated, and one day later, she underwent a redo MVR operation. Extracorporeal membrane oxygenation was discontinued 4 days later. Discussion: Dysfunctional prosthetic valves leading to CS may benefit from a redo cardiac operation supported by a perioperative VA-ECMO to optimize haemodynamic status. Despite the results from risk prediction scores, this approach has the potential to reduce operative mortality in initial inoperable patients and allow a definitive redo cardiac surgery.

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La estenosis aórtica severa sintomática que se presenta en pacientes de alto o mediano riesgo quirúrgico puede ser abordada de manera percutánea con reemplazos valvulares aórticos transcateter. Existe sólida evidencia de resultados favorables en estos pacientes con un perfil de seguridad adecuado. El abordaje transfemoral es el más utilizado y ha demostrado ser más seguro en comparación a los abordajes torácicos. Sin embargo, desde mitades de la década pasada el abordaje transcaval se ha convertido en una opción en los pacientes que presentan un riesgo quirúrgico alto y que presentan una vasculatura inadecuada para un abordaje transfemoral seguro. Presentamos el caso de un paciente de 65 años en quien se empleó este abordaje dado a su alto riesgo quirúrgico e inaccesibilidad para realizar un abordaje transfemoral.

Severe symptomatic aortic stenosis in patients with high surgical risk can be addressed percutaneously with transcatheter aortic valve replacement (TAVR). There is solid evidence of favorable results with an adequate safety profile in these patients. The transfemoral approach is the most widely used and has shown to be safer compared to thoracic approaches. Though, since the middle of the last decade, the transcaval approach has become an option in patients who present a high surgical risk and who have inadequate vasculature for a safe transfemoral approach. We present the case of a 65-year-old patient in whom this approach was preferred due to his high surgical risk and inaccessibility to perform a transfemoral approach.

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PURPOSE: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. MATERIALS AND METHODS: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/ß=4.5 or 3)) to the CTV(α/ß=4.5) and D2 cm3(α/ß=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. RESULTS: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. CONCLUSION: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

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INTRODUCTION: Pilocytic astrocytoma (PA) is the most common brain tumor that affects the pediatric population. Even though PA is benign and treatment only involves surgery, recurrent or unresectable tumors require chemo- and radiotherapy. Besides BRAF, CDKN2A, or IDH mutations, the hyperactivation of the nuclear factor NF-κB contributes to tumor growth and survival. METHODS: In the present study, we used publicly available data for the in silico analysis of NF-κB subunits (RELA, RELB, REL, NF-κB1, and NF-κB2) expression in PA samples. Besides, in vitro assays were performed to evaluate proliferation, migration, cell death, on the PA cell line Res286 comparing to human primary astrocytes. Sensitization to radiation therapy and temozolomide (TMZ) was also assayed. RESULTS: Our results showed that all the members of the NF-kB family are upregulated in PA datasets compared to normal brain tissues. Moreover, DHMEQ treatment significantly reduced cell growth and motility, while sensitized cells to ionizing radiation and TMZ, as previously seen in high-grade gliomas. CONCLUSIONS: This drug presents a potential application in clinical practice for the treatment of recurrent or inoperable PA. Moreover, its use might assist adjuvant chemotherapy and reduce irradiation doses to avoid toxicity to the surrounding tissues.

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INTRODUCTION: Lung cancer is the most frequent neoplasm in humans. Surgery is considered the best therapeutic approach for stage I non-small lung cell cancer (NSCLC). However, a remarkable amount of patients are considered as inoperable. Stereotactic body radiotherapy (SBRT) has risen as an option for those patients, rendering excellent results in quality of life and survival. MATERIALS AND METHODS: We analyzed clinical studies published between 2002 and 2015 which included SBRT as a treatment modality. Our own clinical series was analyzed as well. The patterns of failure following SBRT were investigated, together with the outcomes and the toxicity observed. RESULTS: SBRT has proven to maintain an excellent local control. The analysis showed the tumor size and the histology as determinant factors for the response to treatment. CONCLUSION: According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.

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Introducción: el cáncer de esófago en Cuba es una de las cinco primeras causas de muerte por tumores. El tratamiento incluye quimioterapia, radioterapia y cirugía, así como el descubrimiento de nuevos blancos potenciales para la inmunoterapia, entre los que se encuentra el receptor del Factor de Crecimiento Epidérmico. El anticuerpo monoclonal cubano AcM HR3 (nimotuzumab) se estudia actualmente a nivel mundial. Objetivo: evaluar la eficacia y seguridad del nimotuzumab combinado con radioquimioterapia en tumores de esófago inoperable en comparación con el tratamiento habitual en los pacientes atendidos por esta enfermedad en el Hospital Hermanos Ameijeiras, durante los meses de diciembre de 2005 a junio 2010. Método: se diseñó un estudio clínico controlado, aleatorizado, abierto con dos grupos de tratamiento, uno con Radioquimioterapia más Bioterapia y otro con Radioquimioterapia. La variable principal fue la respuesta clínica, con que clasifica la reducción del tumor, de acuerdo al criterio RECIST, en: remisión completa, remisión parcial, estabilización de la enfermedad y progresión. La toxicidad evaluó los eventos adversos que presentaron los pacientes en cada uno de los grupos de tratamiento. Resultados: en relación a la respuesta objetiva se obtuvo una mayor proporción en el grupo de nimotuzumab (88,9 por ciento) contra el grupo control (22,2 por ciento), con una diferencia estadísticamente significativa entre ambos grupos de 66,7 por ciento. Fueron frecuentes los eventos tos, insomnio, síntomas gastrointestinales y dolor retroesternal en el grupo tratado, mientras que en el grupo control las molestias gastrointestinales y la astenia fueron las de mayor aparición. Conclusiones: los pacientes tratados con nimotuzumab presentaron un mejor índice de respuesta objetiva y de control de la enfermedad y su administración fue segura al combinarse con la terapia establecida para el tratamiento del cáncer de esófago inoperable según las normas terapéuticas cubanas(AU)

Introduction: esophageal cancer in Cuba is one of the first five causes of death from tumors. The treatment includes chemotherapy, radiotherapy and surgery as well as the discovery of new potential targets for immunotherapy such as the epidermal growth factor receptor. The Cuban monoclonal antibody AcM HR3 (nimotuzumab) is studied at present internationally. Objective: to evaluate the efficacy and safety of nimotuzumab combined with radiochemotherapy in inoperable esophageal tumors and to compare it with the ordinary treatment given to patients seen at Hermanos Ameijeiras hospital from December 2005 to June 2010. Method: open, controlled, randomized clinical study was designed for two groups of patients, one with radiochemotherapy plus biotherapy and the other one with radiochemotherapy. The main variable was the clinical response with which the tumor reduction is classified in accordance with the RECIST criteria: complete remission, partial remission, disease stabilization and progression. Toxicity tests evaluated the adverse events that occurred in patients of each of the groups. Results: regarding the objective response, a higher proportion was reached in the group with nimotuzumab (88,9 percent) against the control group (22,2 percent), with statistically significant difference between both groups of patients equal to 66,7 percent. Cough, insomnia, gastrointestinal problems and retrosternal pain were frequent in the treatment group whereas the control group suffered gastrointestinal disturbances and asthenia more frequently. Conclusions: the patients treated with nimotuzumab presented better index of objective response and of disease control and its administration was safe when combined with the set therapy for treatment of inoperable esophageal cancer in line with the Cuban therapeutic standards(AU)

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PURPOSE: The National Cancer Data Base (NCDB) was analyzed to evaluate practice patterns and the impact of radiotherapy modalities for endometrial cancer treated with primary radiotherapy. METHODS AND MATERIALS: The NCDB was queried for Stage I endometrioid adenocarcinoma patients treated with primary radiotherapy without surgery from 1998 to 2006. Brachytherapy (BT) utilization factors were established using multivariable logistic regression. Log-rank and Cox proportional hazards modeling were used to assess variables impacting survival. RESULTS: A total of 853 patients were analyzed: 23.7%, 31.3%, and 45.0% received BT alone, external beam radiotherapy (EBRT) and BT, or EBRT alone. The BT utilization ranged from 40.5% to 51.9% over time (p=0.70). Lower utilization was associated with advanced age (≥80 years: odds ratio [OR] 0.43, 95% confidence interval [CI] 0.28-0.65, p<0.01) and facilities with volume in the bottom quartile (OR 0.44, 95% CI 0.30-0.66, p<0.01). Utilization was higher among patients living more than 30 miles from the facilities (OR 2.14, 95%CI 1.35-3.42, p<0.01). With 36-month median followup, unadjusted median survivals for EBRT dose of 30Gy or lower, EBRT dose higher than 30Gy, BT, and EBRT+BT were 12.6, 31.1, 44.6, and 57.1 months (p<0.01). After correcting for other factors, higher risk of mortality was seen with EBRT dose of 30Gy or lower (hazard ratio [HR]2.75, 95% CI 1.66-4.55, p<0.01) and EBRT dose higher than 30Gy (HR 1.43, 95% CI 1.07-1.91, p=0.02) compared with EBRT+BT. No difference was seen using BT alone (HR 1.29, 95% CI 0.92-1.79, p=0.14). CONCLUSION: BT utilization for nonsurgically managed endometrial cancer remains low with most patients receiving EBRT alone. Despite concerns of overtreatment in a population with competing causes of death, BT appears to improve survival.

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PURPOSE: Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). METHODS AND MATERIALS: Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1-2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. RESULTS: Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. CONCLUSIONS: Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.

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