Mutational Landscape and Actionable Target Rates on Advanced Stage Refractory Cancer Patients: A Multicenter Chilean Experience.

Major advances in sequencing technologies and targeted therapies have accelerated the incorporation of oncology into the era of precision medicine and "biomarker-driven" treatments. However, the impact of this approach on the everyday clinic has yet to be determined. Most precision oncology reports are based on developed countries and usually involve metastatic, hard-to-treat or incurable cancer patients. Moreover, in many cases race and ethnicity in these studies is commonly unreported and real-world evidence in this topic is scarce. Herein, we report data from a total of 202 Chilean advanced stage refractory cancer patients. Retrospectively, we collected patient data from NGS tests and IHC in order to determine the proportion of patients that would benefit from targeted treatments. Overall >20 tumor types were included in our cohort and 37% of patients (n = 74) displayed potentially actionable alterations, including on-label, off-label and immune checkpoint inhibitor recommendations. Our findings were in-line with previous reports such as the cancer genome atlas (TCGA). To our knowledge, this is the first report of its kind in Latin America delivering real-world evidence to estimate the percentage of refractory tumor patients that might benefit from precision oncology. Although this approach is still in its infancy in Chile, we strongly encourage the implementation of mutational tumor boards in our country in order to provide more therapeutic options for advanced stage refractory patients.

False-Positive 18F-Prostate-Specific Membrane Antigen-1007 PET/CT Caused by Hepatic Multifocal Inflammatory Foci.

ABSTRACT: A 68-year-old man with history of treated prostate cancer was referred to 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT imaging. Moderate bone involvement was observed, with a normal liver tracer uptake. Bone biopsy confirmed metastases of prostate cancer. After therapy adjustment, a follow-up 18F-PSMA-1007 PET/CT revealed good response in bone lesions, although it showed 3 new rounded liver intense uptake foci. Concurrent PSA was 0.6 ng/mL. Liver function tests were normal. PET/CT-guided hepatic biopsy demonstrated no malignant cells, focal inflammation, and steatosis, being possibly the inflammation the cause of false-positive multifocal uptake of 18F-PSMA-1007. Following PET/CT, controls showed a normal liver.

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.

Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach.

Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population.

[Hepatic veno-occlusive disease, idiopathic ulcerative colitis and portal thrombosis. Report of one case]. / Enfermedad veno-oclusiva hepática, colitis ulcerosa idiopática y trombosis portal: comunicación de un caso clínico.

We report a previously healthy 29 years old man, presenting with a sudden episode of abdominal pain, mild jaundice, hepatomegaly and ascites. Magnetic resonance imaging study and liver biopsy were compatible with veno-occlusive disease. Incidentally, an ulcerative colitis and portal vein thrombosis were diagnosed. Anticoagulant treatment was started, with good clinical and radiological response. Veno-occlusive disease of the liver must be suspected In cases of liver failure and ascites associated to procoagulant conditions.

Transfusión de granulocitos en pacientes neutropénicos febriles / Granulocyte transfusion in febrile neutropenic patients

Desde 1996 a la fecha hemos transfundido con granulocitos a 20 pacientes con 21 episodios de neutropenia febril con criterios de extrema gravedad. 14 episodios correspondieron a sepsis con germen conocido y 7 neutropenia febril sin germen aislado. Los pacientes recibieron un promedio de 3.7 aféresis, con 2.17(potencia 10) granulocitos por cada una. Los donantes fueron seleccionados entre familiares directos con estudios rutinarios para la donaci¢n de sangre, los que fueron condicionados con factor estimulante de colonias granulocíticas previa al procedimiento aferético. 15 pacientes sobrevivieron al episodio neutropénico con resolución de cuadro infeccioso. Las reacciones adversas transfucionales en los receptores fueron leves y no hubo complicaciones clínicas en los donantes. Las transfusiones de granulocitos parecen ser efectivas en pacientes con neutropenia febril sin respuesta a antibióticos

Neutropenia febril: complicación frecuente en pacientes sometidos a quimioterapia / Febrile neutropenia: frequent complication in patients subjected to chemotherapy

En pacientes neutropénicos es frecuente la presencia de fiebre e infecciones diversas, sobre todo con recuentos bajos de neutrófilos. Nos interesa precisar las infecciones más frecuentes de estos pacientes en nuestro medio, la posibilidad de profilaxis y la evolución de estos. Se estudian 77 pacientes que presentaron neutropenia después de ser sometidos a quimioterapia (QMT) en el Hospital F.A.CH. de Santiago, entre Enero de 1986 y Mayo de 1993. Se revisaron los antecedentes clínicos, valor de neutropenia, aparición de fiebre durante el período neutropénico, antibióticos utilizados, foco y agentes infecciosos aislados. La indicación más frecuente para realizar QMT, fueron los linfomas, la incidencia de neutropenia post QMT, fue de 63,1 porciento. Dentro de los pacientes neutropénicos se registró fiebre en un 39 porciento, con mayor frecuencia bajo un recuento de neutrófilos de 500 por mm3. El esquema antibiótico más usado, fue el de una Cefalosporina de IIIa generación con un Aminoglucósido y dentro de los agentes aislados, predominaron los Bacilos Gram (-), también las formas Cocaceas Gram (+) y en menor número los hongos. Se concluye que la QMT, favorece la aparición de neutropénia y que esta última, predispone a infecciones diversas, graves, sobre todo con recuentos bajos de neutrófilos, por lo que se hace imperioso tomar medidas especiales en este tipo de pacientes, como tratamiento antibiótico profiláctico o terapéutico precoz. No se puede concluir respecto al uso de G-CSF o GM-CFF, ya que no fueron utilizados en todos los casos en que habrían estado indicados. Sin embargo, la recuperación del recuento de neutrófilos en los pacientes en que sí se utilizó, se logró en aproximadamente 30 días, igual a lo que ocurrió en los pacientes en los que no se administró