Aplicación clínica de la [18F]FDG PET/TC en el linfoma folicular / Clinical application of [18F]FDG PET/CT in follicular lymphoma

El objetivo de este trabajo fue revisar el papel de la [18F]FDG PET/TC en el linfoma folicular (LF). Tras confirmarse que a pesar de su carácter indolente este tipo de linfoma habitualmente muestra avidez por el radiotrazador, la [18F]FDG PET/TC fue cobrando una importancia progresivamente mayor hasta ser considerada como la técnica de elección para su estadificación, re-estadificación y valoración de respuesta al tratamiento. Múltiples estudios han demostrado el impacto que supone en el manejo de estos pacientes (puede cambiar el estadio de la enfermedad en una proporción significativa de casos y condicionar modificaciones en el tratamiento), su superioridad respecto a la TC (principalmente por la capacidad para distinguir tejido tumoral viable de tejido fibrótico residual) y su valor pronóstico. Esto último se atribuyó inicialmente de forma exclusiva al grado de respuesta metabólica alcanzado tras el tratamiento, que ha probado ser un factor predictivo fuerte e independiente de supervivencia libre de progresión (SLP) y supervivencia global (SG), de modo que una [18F]FDG PET/TC negativa podría considerarse una garantía para los pacientes con LF con elevada carga tumoral. No obstante, la obtención de parámetros metabólicos semicuantitativos como el volumen metabólico tumoral o la glucólisis total de la lesión podría también aportar información a este respecto y ayudarnos potencialmente a identificar a los pacientes de mal pronóstico antes del inicio del tratamiento, de forma que se pueda adecuar el manejo y seguimiento al riesgo del paciente (AU)

The objective of the present paper was to review the clinical application of [18F]FDG PET/CT in follicular lymphoma (FL). Once it was clear that, despite it's characterized as indolent, this type of lymphoma usually shows a high [18F]FDG avidity, PET/CT became more important and it's now considered the standard technique in staging, re-staging and response evaluation. Many studies have shown its impact on the management of patients (as it can change the stage in a significant proportion of cases and lead to treatment modifications), its superiority over CT (mainly because it's able to distinguish fibrosis in residual masses from viable tumor) and its prognostic value. The latter was initially associated only to the degree of metabolic response, which has proved to be a strong and independent predictive factor in terms of disease-free survival (DFS) and overall survival (OS). Thus, a negative PET/CT scan could be considered a guarantee in high-tumor-burden follicular lymphoma patients. However, semiquantitative parameters such as metabolic tumor volume or total lesion glycolysis, may also provide useful information and help us to identify patients with poor prognosis, guiding a risk-adjusted management and follow-up (AU)

Clinical application of [18F]FDG PET/CT in follicular lymphoma.

The objective of the present paper was to review the clinical application of [18F]FDG PET/CT in follicular lymphoma (FL). Once it was clear that, despite it is characterized as indolent, this type of lymphoma usually shows a high [18F]FDG avidity, PET/CT became more important and it's now considered the standard technique in staging, re-staging and response evaluation. Many studies have shown its impact on the management of patients (as it can change the stage in a significant proportion of cases and lead to treatment modifications), its superiority over CT (mainly because it's able to distinguish fibrosis in residual masses from viable tumor) and its prognostic value. The latter was initially associated only to the degree of metabolic response, which has proved to be a strong and independent predictive factor in terms of disease-free survival (DFS) and overall survival (OS). Thus, a negative PET/CT scan could be considered a guarantee in high-tumor-burden follicular lymphoma patients. However, semiquantitative parameters such as metabolic tumor volume or total lesion glycolysis, may also provide useful information and help us to identify patients with poor prognosis, guiding a risk-adjusted management and follow-up.

Linfoma folicular duodenal primario: reporte de caso y revisión de la literatura / Primary duodenal follicular lymphoma: Case report and literature review

Resumen Los linfomas primarios del tracto gastrointestinal son infrecuentes; sin embargo, son la presentación extranodal más común de los linfomas no Hodgkin. El 30 % de los linfomas no Hodgkin corresponde a linfomas foliculares y, a su vez, cerca del 10 % de los linfomas foliculares se origina en el tracto gastrointestinal. Se han descrito factores de riesgo para el desarrollo de linfomas gastrointestinales como infección por Helicobacter pylori, inmunosupresión posterior a trasplante de órganos sólidos, enfermedad inflamatoria intestinal e infección por virus de la inmunodeficiencia humana (VIH). El linfoma duodenal folicular se reconoció como una variante del linfoma folicular en 2016 según la clasificación de la Organización Mundial de la Salud (OMS), al considerar que se trata de una condición con características biológicas y clínicas particulares. Su diagnóstico suele ser incidental o se pueden presentar síntomas leves e inespecíficos. El grado histológico suele ser bajo y el curso clínico, benigno; por lo que en gran parte de los casos se ha adoptado el manejo expectante como una opción. Otras terapias con similar efectividad son la radioterapia, el uso de rituximab y la inmunoquimioterapia. No existe a la fecha suficiente evidencia para generar un protocolo único de manejo para esta patología.

Abstract Primary gastric lymphomas are rare diseases; however, they are the most common extranodal presentation of non-Hodgkin lymphomas. 30% of non-Hodgkin lymphomas correspond to follicular lymphomas and at the same time, nearly 10% of follicular lymphomas are produced in the gastrointestinal tract. Risk factors for gastric lymphomas such as Helicobacter pylori infection, immunosuppression after solid organ transplantation, inflammatory bowel disease, and human immunodeficiency virus (HIV) infection were described. Follicular duodenal lymphoma was recognized as a variant of follicular lymphoma in 2016 according to the World Health Organization (WHO) classification, considering that it is a condition with special biological and clinical characteristics. Its diagnosis is usually incidental or mild and nonspecific symptoms may occur. The histological grade is usually low, and the clinical course is benign; Therefore, in most cases, expectant treatment has been adopted as an option. Other therapies with similar effectiveness are radiotherapy, the use of rituximab, and immunochemotherapy. There is not enough evidence to date to generate a single management protocol for this pathology.

Metabolic Reprogramming of Non-Hodgkin's B-Cell Lymphomas and Potential Therapeutic Strategies.

Metabolism is a wide and general term that refers to any intracellular pathways the cell utilizes in order to satisfy its energetic demand and to support cell viability and/or division. Along with phenotypic changes, all mammalian cells including immune cells modulate their metabolic program in order to reach their effector functions. Exacerbated metabolism and metabolic flexibility are also hallmarks of tumor initiation and of tumor cell progression in a complex tumor microenvironment. Metabolic reprogramming is mainly directed by the serine/threonine kinase mTOR (mammalian target of rapamycin). mTOR exists in two structurally and functionally distinct complexes, mTORC1 and mTORC2 that coordinate environmental signals and metabolic/anabolic pathways to provide macromolecules and energy needed for survival and growth. Activation of mTORC1 is required during development, differentiation and activation of immune cells. Aberrant and persistent activation of mTORC1 is often observed in malignant B cells such as Non-Hodgkin's (NH) B-cell lymphomas. Here, we review recent insights on cell metabolism and on basic mechanisms of mTORC1 regulation and metabolic functions. We highlight the distinct mechanisms driving mTORC1 activation in the three most-common types of NH B-cell lymphomas (Diffuse Large B Cell Lymphomas, Follicular Lymphomas, and Mantle Cell Lymphomas), for which the first generation of mTORC1 inhibitors (rapalogs) have been extensively evaluated in preclinical and clinical settings. Finally, we discuss the reasons for limited clinical success of this therapy and focus on potential therapeutic strategies targeting metabolic pathways, upstream and downstream of mTORC1, that can be combined to rapalogs in order to improve patient's outcome.