Valor pronóstico de los criterios PERCIST y los parámetros metabólicos de la PET/TC en pacientes con cáncer de esófago tras tratamiento neoadyuvante / Prognostic value of PERCIST and PET/CT metabolic parameters in patients with esophageal cancer after neoadjuvant treatment

Objetivo Valorar la utilidad clínica de los criterios PERCIST y de los cambios en los parámetros cuantitativos de la PET/TC con [18F]FDG como factores pronósticos para la supervivencia libre de progresión y la supervivencia cáncer-específica en pacientes con cáncer de esófago tratados mediante quimiorradioterapia. Material y métodos Se valoraron retrospectivamente 50 pacientes (48 hombres) diagnosticados de cáncer de esófago durante un intervalo de 7,5 años. Se utilizaron los criterios PERCIST para valorar la respuesta a la neoadyuvancia. Asimismo, se determinaron las variaciones del SUV máximo, volumen metabólico tumoral y glucólisis tumoral total entre los estudios PET/TC pre- y postratamiento. Las curvas ROC, el método de Kaplan-Meier y el modelo de regresión de Cox se aplicaron para el análisis de factores pronósticos y curvas de supervivencia. Resultados El seguimiento medio fue de 26,8 meses, produciéndose 40 recurrencias-progresiones y 41 muertes. El análisis de supervivencia mostró curvas de supervivencia cáncer-específica con diferencias estadísticamente significativas en relación con los criterios PERCIST y la variación del volumen metabólico tumoral y la glucólisis tumoral total. Los criterios PERCIST fueron el único factor predictivo independiente en el análisis multivariante. Ni el SUV máximo ni el tamaño tumoral fueron predictores para ninguno de los criterios de evaluación. Conclusión La aplicación de los criterios PERCIST, así como el cambio de volumen metabólico tumoral y glucólisis tumoral total de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia cáncer-específica en pacientes de nuestro entorno tratados por cáncer de esófago. Los resultados podrían ayudar a personalizar el tratamiento (AU)

Aim To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival in patients with esophageal cancer treated by chemoradiotherapy. Material and methods Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV, metabolic tumor volume and total lesion glycolysis between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. Results The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in cancer-specific survival curves for PERCIST criteria and variation of metabolic tumor volume and total lesion glycolysis. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither maximum SUV nor tumor size were predictors for any of the assessment criteria Conclusion Application of PERCIST criteria as well as change in metabolic tumor volume and total lesion glycolysis from PET/CT studies proved to be prognostic factors for cancer-specific survival in patients in our setting treated for esophageal cancer. The results could help to personalize treatment (AU)

Evaluación del valor pronóstico de los parámetros volumétricos metabólicos calculados con la 18F-FDG PET/TC y su valor añadido a las características moleculares en pacientes con linfoma B difuso de células grandes / Evaluation of the prognostic value of the metabolic volumetric parameters calculated with 18F-FDG PET/CT and its value added to the molecular characteristics in patients with diffuse large b-cell lymphoma

Introducción y objetivos: El volumen metabólico tumoral (VMT) y la glicólisis total de la lesión (TLG) son predictores pronósticos en los pacientes con linfoma B difuso de células grandes (LBDCG). El objetivo del presente estudio es evaluar el impacto pronóstico de los parámetros volumétricos basales calculados con la tomografía por emisión de positrones/tomografía computarizada con 18F-fluorodesoxiglucosa (18F-FDG PET/TC) y su valor agregado a las características moleculares en pacientes con LBDCG tipo no especificado (NOS). Metodología: Se trata de un estudio retrospectivo observacional, en el que se incluyeron 35 pacientes sometidos a un 18F-FDG PET/TC basal previo al tratamiento. Se realizó un análisis univariable de los parámetros volumétricos (VMT y TLG), estudio inmunohistoquímico y traslocaciones cromosómicas. El método para el cálculo de los parámetros volumétricos fue el umbral SUV 2,5. La comparación entre los modelos predictivos se seleccionó en función del valor de criterio de información de Akaike (AIC), bayesiano (BIC) y C de Harrell, después de realizar un modelo de regresión de riesgos proporcionales de Cox. Además, se realizó un análisis univariable de los parámetros volumétricos, según los datos del estudio inmunohistoquímico utilizando la prueba de Wilcoxon-Mann-Whitney. Resultados: Al realizar un análisis univariable se evidenció que el VMT y la TLG son predictores de la supervivencia libre de progresión (SLP) y de la supervivencia global (SG), con una alta capacidad de discriminación. El añadir el VMT y la TLG al estudio inmunohistoquímico y a la traslocación cromosómica proporcionó un mejor valor pronóstico a la SLP y SG en los pacientes diagnosticados con LBDCG tipo NOS. Así mismo, se evidenció que los valores de los parámetros volumétricos eran menores en los pacientes que presentaron un fenotipo células B centro germinal (GCB) frente a los pacientes con fenotipo células B activadas (ABC) que presentaron valores mayores (AU)

Introduction and objectives: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are prognostic predictors in patients with diffuse large B-cell lymphoma (DLBCL). The objective of this study is to evaluate the prognostic impact of the baseline volumetric parameters calculated with positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and its added value to the molecular characteristics in patients with DLBCL not otherwise specified (NOS). Methodology: This is a retrospective observational study, which included 35 patients who underwent a baseline 18F-FDG PET/CT prior to treatment. A univariate analysis of the volumetric parameters (MTV and TLG), immunohistochemical study and chromosomal translocations were performed. The method for calculating the volumetric parameters was the SUV 2.5 threshold. The comparison between the predictive models was selected based on the information criterion value of Akaike (AIC), bayesian (BIC) and Harrell's C, after performing a Cox proportional hazards regression model. In addition, a univariate analysis of the volumetric parameters was performed according to the data of the immunohistochemical study using the Wilcoxon-Mann-Whitney test. Results: A univariate analysis revealed that VMT and TLG are predictors of progression-free survival (PFS) and overall survival (OS), with a high discrimination capacity. Adding VMT and TLG to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS. Likewise, it was evidenced that the values of the volumetric parameters were lower in patients who presented a germinal center B cell phenotype (GCB) compared to patients with an activated B cell phenotype (ABC) who presented higher values. Conclusion: MTV and TLG added to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS (AU)

Valor predictivo de los índices 18F-FDG PET/TC sobre la carga tumoral residual en pacientes con cáncer de mama extenso tratadas con quimioterapia neoadyuvante / Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy

Objetivo: Investigamos la correlación entre los índices de PET/TC con 18F-FDG y la respuesta patológica en el cáncer de mama tratado con quimioterapia neoadyuvante (QNA), que se puntuó con el sistema de carga de cáncer residual (RCB) después de la cirugía. Nuestro objetivo es detectar antes una carga extensa de cáncer residual mediante el uso de los índices de PET/TC. Métodos: Se recuperaron las características de las pacientes de forma retrospectiva. Se calculó el valor máximo de captación estándar (SUVmáx), el volumen metabólico del tumor (MTV) y los índices de glucólisis total de la lesión (TLG), así como la tasa de reducción (RR) entre la línea de base y la evaluación intermedia, con la exploración FDG PET/TC. Todos los pacientes fueron evaluados según las puntuaciones RCB después de la cirugía. Las respuestas patológicas y los resultados de las mediciones de PET/TC se analizaron con parámetros demográficos y clínicos. Resultados: Un total de 95 pacientes fueron incluidos en el estudio. Según las respuestas patológicas, la distribución de RCB-0, -1, -2, -3 fue de 13 (13,7%), 11 (11,6%), 30 (31,6%) y 41 (43,2%), respectivamente. La supervivencia libre de enfermedad fue significativamente menor en el grupo RCB-3 en comparación con el grupo de respuesta patológica (p=0,01). Según el análisis multivariante, se determinó que el RR del SUVmáx era una variable independiente que predecía la RCB extensa con un valor de corte óptimo del 86% (p<0,05). Conclusiones: Determinamos el RR de SUVmáx como un factor independiente para predecir la carga tumoral residual extensa. Creemos que el RR de SUVmáx es suficiente para predecir la respuesta patológica en la práctica diaria. Además, las mediciones de MTV y TLG no contribuyen adicionalmente al SUVmáx por sí solas y pueden causar una pérdida de trabajo innecesaria (AU)

Aim: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. Methods: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. Results: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB-0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB-3 group compared to the pathological responder group (P=.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (P<.05). Conclusions: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss (AU)

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)

Evaluation of the prognostic value of the metabolic volumetric parameters calculated with 18F-FDG PET/CT and its value added to the molecular characteristics in patients with diffuse large B-cell lymphoma.

INTRODUCTION AND OBJECTIVES: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are prognostic predictors in patients with diffuse large B-cell lymphoma (DLBCL). The objective of this study is to evaluate the prognostic impact of the baseline volumetric parameters calculated with positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and its added value to the molecular characteristics in patients with DLBCL not otherwise specified (NOS). METHODOLOGY: This is a retrospective observational study, which included 35 patients who underwent a baseline 18F-FDG PET/CT prior to treatment. A univariate analysis of the volumetric parameters (MTV and TLG), immunohistochemical study and chromosomal translocations were performed. The method for calculating the volumetric parameters was the SUV 2.5 threshold. The comparison between the predictive models was selected based on the information criterion value of Akaike (AIC), bayesian (BIC) and Harrell's C, after performing a Cox proportional hazards regression model. In addition, a univariate analysis of the volumetric parameters was performed according to the data of the immunohistochemical study using the Wilcoxon-Mann-Whitney test. RESULTS: A univariate analysis revealed that VMT and TLG are predictors of progression-free survival (PFS) and overall survival (OS), with a high discrimination capacity. Adding VMT and TLG to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS. Likewise, it was evidenced that the values of the volumetric parameters were lower in patients who presented a germinal center B cell phenotype (GCB) compared to patients with an activated B cell phenotype (ABC) who presented higher values. CONCLUSION: MTV and TLG added to the immunohistochemical study and chromosomal translocation provided a better prognostic value for PFS and OS in patients diagnosed with DLBCL-NOS.

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.

Evaluation of the prognostic value of different methods of calculating the tumour metabolic volume with 18F-FDG PET/CT, in patients with diffuse large cell B-cell lymphoma. / Evaluación del valor pronóstico de los diferentes métodos de cálculo del volumen metabólico tumoral con 18F-FDG PET/TC, en pacientes con linfoma B difuso de células grandes.

INTRODUCTION AND OBJECTIVES: Metabolic tumor volume (MTV) is a promising indicator of prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of the present study is to evaluate the different methods for the calculation of the basal metabolic tumor volume with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the patients with DLBCL, relating each one of the volumes measured with progression-free survival (PFS) and overall survival (OS). METHODOLOGY: This is a retrospective analytical cohort study, in which 34 patients underwent to 18F-FDG PET/CT baseline prior to treatment. We compared three SUV thresholds 2.5, SUV 40% of the maximum SUV and SUV mean hepatic uptake (PERCIST) for the calculation of MTV and total lesion glycolysis (TLG) biomarkers, relating them to the PFS and OS. The best predictive model was selected based on the Akaike's information criterion (AIC) after performing a Cox proportional hazards regression. RESULTS: In relation to the PFS, they show statistically significant differences: MTV 2.5, TLG 2.5, MTV 40, TLG 40, MTV and TLG calculated with the PERCIST threshold. Among these, the one that has a lower AIC is MTV 2.5, so it is considered the best parameter to predict the PFS. With respect to OS, it shows statistically significant differences: MTV 2.5, VMT and TLG calculated with the PERCIST threshold. Among these three, the one with the lowest AIC is MTV 2.5, which is why it is considered the best parameter to predict OS. In addition, a higher value of MTV and total tumor glycolysis (TLG), is associated with worse PFS and OS CONCLUSION: The MTV calculated with the threshold SUV 2.5 seems to be the best parameter to predict PFS and OS in patients diagnosed with DLBCL with 18F-FDG PET/CT.

Prognostic significance of metabolic tumor volume and total lesion glycolysis in patients with advanced cervical carcinoma. / Significación pronóstica del volumen metabólico tumoral y de la glucólisis tumoral total en pacientes con cáncer cervical avanzado.

AIM: 18-Fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET/CT) is considered to be the most accurate image method of detection of node or distant metastases in cervical cancer. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT are volumetric measurements of tumor cells with increased 18F-FDG uptake. The prognostic value of MTV and TLG in patients with advanced cervical cancer (ACC) were evaluated. METHODS: 38 patients with ACC from one tertiary university hospital underwent 18F-FDG PET/CT between June 2009 and December 2015. Clinicopathologic factors and various PET parameters were analyzed to evaluate their relationship with recurrence-free survival (RFS) and overall survival (OS). These parameters were: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, of the pelvic nodes, of the paraaortic nodes and the metabolic volume of the metastases if any. RESULTS: A total of 38 patients with ACC fulfilled the inclusion criteria. All of them underwent a 18F-FDG PET/CT before definitive chemoradiotherapy. In the univariate analyses higher tumor size, pelvic lymph node metastasis and both MTV and TLG showed a significant association with OS and with RFS (MTV HR=1.55, p=0.011 and TLG HR=1.43, p=0.017 for RFS and MTV HR=1.82, p=0.006 and TLG HR=1.67, p=0.007 for OS). CONCLUSION: Pretreatment TLG sum and MTV sum seem to be independent prognostic factors for OS and RFS in patients with advanced cervical cancer treated with definitive chemoradiotherapy and they are better than the classic measurement of SUVmax.

Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging. / Papel pronóstico del volumen metabólico tumoral y de la glucólisis tumoral total en los estudios 18F-FDG PET/TC de estadificación del cáncer localmente avanzado de mama.

OBJECTIVE: To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. MATERIAL AND METHODS: Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). RESULTS: Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm3, TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). CONCLUSIONS: In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data.