BackgroundCoagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.Patients and methodsWe carried out a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events.ResultsIn RASTEN, 390 patients were randomized over an 8-year period (2008–2016), of whom 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin [hazard ratio (HR), 1.11; 95% confidence interval (CI) 0.89–1.38; P = 0.36 and HR, 1.18; 95% CI 0.95–1.46; P = 0.14, respectively]. Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR, 0.31; 95% CI 0.11–0.84; P = 0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.ConclusionLMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted.

Coagulation activation and venous thromboembolism (VTE) are hallmarks of cancer; however, there is an unmet need of improved biomarkers for individualized anticoagulant treatment. The present sub-study of the RASTEN trial was designed to explore the role of coagulation biomarkers in predicting VTE risk and outcome in a homogenous cancer patient population. RASTEN is a multicenter, randomized phase-3 trial investigating the survival effect of low molecular weight heparin enoxaparin when added to standard treatment in newly diagnosed small cell lung cancer (SCLC) patients. Plasma collected at baseline, during treatment, and at follow-up was used in this ad hoc sub-study (N = 242). Systemic coagulation was assessed using four assays reflecting various facets of the coagulation system: Total tissue factor (TF); extracellular vesicle associated TF (EV-TF); procoagulant phospholipids (PPL); and thrombin generation (TG). We found small variations of biomarker levels between baseline, during treatment and at follow-up, and appeared independent on low molecular weight heparin treatment. Overall, none of the measured biomarkers at any time-point did significantly associate with VTE incidence, although increased total TF at baseline showed significant association in control patients not receiving low molecular weight heparin (P = 0.03). Increased TG-Peak was significantly associated with decreased overall survival (OS; P = 0.03), especially in patients with extensive disease. Low baseline EV-TF predicted a worse survival in the low molecular weight heparin as compared with the control group (HR 1.42; 95% CI 1.04–1.95; P = 0.03; P for interaction = 0.12). We conclude that the value of the analyzed coagulation biomarkers for the prediction of VTE risk was very limited in SCLC patients. The associations between TG-Peak and EV-TF with patient survival and response to low molecular weight heparin therapy, respectively, warrant further studies on the role of coagulation activation in SCLC aggressiveness.

Black esophagus due to acute necrotizing esophagitis. Report of one case Acute esophageal necrosis, which presents as a black esophagus on endoscopy, is an uncommon occurrence. It is defined as a dark pigmentation of the esophagus associated with histologic mucosal necrosis. We report a 75-year-old men who developed black esophagus due to acute esophageal necrosis caused by septicemia. The patient had a favorable evolution (Rev Méd Chile 2009; 137: 672-4).

Systemic lymphoma that involves the aorta is called periaortic lymphoma, and may be misdiagnosed clinically or in CT scanE l linfoma no Hodgkin (LNH) habitualmente se presenta como una enfermedad sistémica, con linfadenopatías, fiebre y pérdida de peso. En el tórax puede presentarse con masas pulmonares o derrame pleural 1,2 . El compromiso extrapleural es raro 3 . En el abdomen se observan comúnmente grandes masas o linfadenopatías. El linfoma sisté-mico que compromete la pared aórtica se llama linfoma periaórtico (LP) y en la tomografía axial computada (TAC) puede ser confundido con un aneurisma de aorta torácica, disección o un hematoma intramural [4][5][6][7] . Es una entidad poco frecuente, la mayoría son LNH y cuando el LP se presenta, habitualmente lo hace sin linfadenopatías.Reportamos el primer caso de un linfoma periaórtico tóraco-abdominal que simula un sín-drome aórtico agudo (SAA). CASO CLÍNICOMujer de 70 años, con antecedentes de hipertensión arterial y tabaquista de 20 paquetes/año, en quien un LNH sistémico se presentó con características clínicas de un SAA, en su variante CASOS CLÍNICOS

size in a Bayesian predictive probability design. Result: Among the 38 patients, the median age was 63 years (range 44-76) and median line of prior chemotherapies 1 (range 1-3). At the time of analysis, each patient was followed up for at least 12 weeks. The most common grade 3 or higher AEs included anemia (34.2%), hyponatremia (10.5%), lymphopenia (10.5%), chronic obstructive pulmonary disease (5.3%), increased GGT (5.3%) and increased lipase (5.3%). DCR at 12 weeks was 29%. Confirmed responses included one partial response and one complete response. Three additional patients had unconfirmed responses. The updated primary and secondary endpoints, as well as biomarker and PK data will be presented. Conclusion: Although AEs of all grades were seen commonly, the combination of olaparib and durvalumab was relatively well tolerated, as most of the AEs were attributed to underlying disease. While efficacy of the combination in this SCLC population did not reach the target DCR and is below the futility boundary (<40%), a minority of patients obtained significant benefit and will be followed up for further clinical and translational analyzes.