Distribution of molecular subtypes of advanced lung adenocarcinoma and clinical outcomes in a center of Argentina

The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.

La prevalencia de alteraciones en oncogenes en adenocarcinoma de pulmón varía en nuestra región. El objetivo fue describir la prevalencia de mutaciones en KRAS, BRAF y EGFR y las translocaciones de ALK en pacientes con adenocarcinoma de pulmón y estudiar la supervivencia de acuerdo a subtipos moleculares. Se incluyeron pacientes con biopsias adecuadas para el estudio. Se evaluó el estado mutacional de KRAS, BRAF y EGFR por secuenciación con la técnica de Sanger. Las translocaciones de ALK se estudiaron por hibridación in situ por fluorescencia (FISH) e inmunohistoquimica (IHQ) contra ALK (clones D5F3 y 5A4). De 118 pacientes evaluados, se incluyeron 84 (72%) con análisis molecular completo. Se detectaron mutaciones de KRAS en 16 muestras (19%), EGFR en 11 (13%), y BRAF en 1 muestra (1%). Se detectaron rearreglos de ALK en 3 muestras (4%). La mediana de seguimiento de los pacientes fue de 42.4 [rango intercuatilo (RIC): 27.0-64.2] meses. Globalmente, la mediana de supervivencia en la población fue 10.3 [RIC: 5.6-20.2] meses y fue de 10.8 [RIC: 6.0 20.3] meses en pacientes sin alteraciones moleculares detectables. La mediana de supervivencia de los pacientes con mutación en KRAS fue de 9.6 [RIC: 3.7-16.1] meses (HR: 1.08; p = 0.82) y 32.5 [RIC: 19.6-38.4] meses en el grupo con rearreglos de ALK o mutaciones en EGFR tratados con inhibidores de tirosina quinasa (HR: 0.27; p = 0.03). En conclusión, la prevalencia de alteraciones moleculares en nuestra población fue similar a otros países occidentales.

Factores de mal pronostico en pacientes internados con neutropenia al inicio del episodio febril / Prognostic risk factors for serious complications in an inpatient population with neutropenia at the onset of a febrile episode

Los pacientes con neutropenia y fiebre constituyen una población heterogénea con riesgo variable para el desarrollo de complicaciones serias y mortalidad. El objetivo de este trabajo es identificarfactores que, presentes al ingreso, estuvieran asociados a mayor riesgo de complicaciones graves en pacientesque se internan por neutropenia y fiebre. Se trata de un estudio de seguimiento de una cohorte de 238 episodios de neutropenia y fiebre (neutrófilos <1000/mm3 y T>38.3 °C) en 167 pacientes internados en sala general en nuestra institución desde 1997 a 2004. Ochenta y dos por ciento de los pacientes tenían enfermedad hematológica, 14% tumores sólidos y 4% no asociados a quimioterapia. Se registraron 67 eventos adversos (46% de insuficiencia renal, 27% de hipotensión refractaria, 15% de insuficiencia respiratoria y 12% con sangrado mayor). Se hallaron diferencias significativas en presencia de comorbilidades previas, temperatura mayor a 39 °C, frecuencia cardíaca mayor a 120 latidos por minuto, frecuencia respiratoria mayor a 24 por minuto, tensión arterial sistólica menor a 90 mm Hg, presencia de 3 o más valores de laboratorio alterados al ingreso, presencia de foco clínico y hemocultivos positivos. En el análisis multivariado de regresión logística mantuvieron asociación independiente con mayor riesgo de eventos graves: hipotensión arterial sistólica (OR=7, p<0.01), comorbilidades (OR=8.5, p=0.02), taquipnea (OR=2.8, p=0.01), y presencia de foco clínico (OR=2.1, p=0.03)

Patients with neutropenia and fever conform a heterogeneouspopulation with a variable risk of serious complications and mortality. The goal of this study was to identifyprognostic risk factors present at the beginning of the episode, for adverse events and serious complications inpatients admitted in a general ward with fever and neutropenia. A cohort of 238 episodes with neutropenia andfever (neutrophils <1000/mm3 and T>38.3 °C) in 167 patients admitted to our general hospital between 1997and 2004 was followed. Eighty two percent of the patients had hematologic malignancies, 14% solid tumors and4% were not associated with chemotherapy. Sixty seven adverse events were registered (46% renal insufficiency, 27% refractory hypotension, 15% respiratory insufficiency and 12% major bleeding). Significant differences werefound in presence of current co-morbidities, body temperature >39 °C, heart rate >120 beats per minute, respiratory rate >24 per minute, systolic blood pressure <90 mm Hg, presence of 3 or more altered laboratory values, presenceof a clinical site of infection and positive blood cultures. The logistic regression multivariate analysis showedthat the following characteristics were independently associated with adverse events: systolic blood pressure<90 mm Hg (OR=7, p<0.01), current co-morbidities (OR=8.5, p=0.02), respiratory rate >24 per minute (OR=2.8, p=0.01), and the presence of a clinical site of infection (OR=2.1, p=0.03). The presence of systolic hypotension, high respiratory rate, current co-morbidities and a clinical site of infection at the time of admission were identified predictors of subsequent serious complications in patients admitted with fever and neutropenia in a general ward