Publication: PET-TC 18F-FDG en la evaluación de respuesta a quimioterapia neoadyuvante en el cáncer de mama
Authors
Ibáñez Ibáñez, María José
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Escuela Internacional de Doctorado
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Navarro Fernández, José Luis ; Piñero Madrona, A.
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
Introducción
El cáncer de mama continúa siendo la neoplasia más frecuente en mujeres y una de las principales causas de mortalidad oncológica a nivel mundial. La quimioterapia neoadyuvante (QTN), también denominada terapia sistémica primaria, ha permitido reducir el tamaño tumoral, favorecer la cirugía conservadora y evaluar de forma directa la respuesta al tratamiento. La obtención de una respuesta patológica completa (RPc) se asocia con un mejor pronóstico, especialmente en subtipos de mayor agresividad biológica como los tumores HER2 positivos y triple negativos.
Tradicionalmente, la valoración de la respuesta a la QTN se ha basado en técnicas anatómicas como la resonancia magnética. Sin embargo, estas presentan limitaciones para detectar cambios metabólicos tempranos o enfermedad residual mínima. En este contexto, el PET-TC con 18F-FDG (Tomografía por Emisión de Positrones-Tomografía Computerizada con 18F-Fluorodesoxiglucosa) aporta información funcional sobre la actividad metabólica tumoral. Parámetros como el SUV, el volumen tumoral metabólico (MTV) y la glucólisis tumoral total (TLG) podrían anticipar la respuesta histopatológica final y contribuir a estrategias terapéuticas más precisas.
Objetivos
El objetivo principal fue determinar el valor predictivo de la respuesta metabólica evaluada mediante PET-TC con 18F-FDG al finalizar la QTN para anticipar la RPc en pacientes con cáncer de mama. Como objetivos secundarios, se analizó la correlación entre la respuesta metabólica en tumor primario y ganglios y la respuesta patológica final, la capacidad predictiva de distintos parámetros metabólicos y la influencia del subtipo molecular.
Material y métodos
Se realizó un estudio observacional prospectivo en pacientes con cáncer de mama candidatas a tratamiento sistémico primario. Se efectuaron dos estudios PET-TC con 18F-FDG: uno basal previo a la QTN y otro tras su finalización, antes de la cirugía. La respuesta metabólica se evaluó de forma cualitativa y mediante parámetros semicuantitativos (SUV, MTV y TLG). La respuesta patológica se valoró mediante el sistema Residual Cancer Burden. Se emplearon análisis de concordancia, cálculos de sensibilidad, especificidad y valores predictivos, así como modelos de regresión logística uni y multivariante.
Resultados
De las 121 pacientes inicialmente incluidas, 105 cumplieron los criterios de estudio. El 37,1 % alcanzó RPc y el 53,3 % presentó respuesta metabólica completa. El PET-TC mostró una sensibilidad del 92 %, especificidad del 70 % y un valor predictivo negativo del 94%, con concordancia moderada. El MTV residual post-QTN, actuaron como predictores independientes de respuesta completa. La correlación fue más sólida en los subtipos HER2 positivos y triple negativos que en los tumores luminales.
Conclusiones
El PET-TC con 18F-FDG al finalizar la QTN mostró un alto rendimiento para anticipar la RPc en cáncer de mama, destacando su elevado valor predictivo para detectar enfermedad residual. El MTV residual se confirmó como predictor independiente de respuesta, con un rendimiento dependiente del subtipo molecular. Estos resultados apoyan el papel del PET-TC como herramienta complementaria en la evaluación de respuesta y en el desarrollo de estrategias terapéuticas personalizadas.
Introduction Breast cancer remains the most common malignancy among women and one of the leading causes of cancer-related mortality worldwide. The incorporation of neoadjuvant chemotherapy (NAC), also referred to as primary systemic therapy, has enabled tumour downstaging, facilitated breast-conserving surgery, and allowed direct assessment of treatment response. Achieving a pathological complete response (pCR) is associated with improved prognosis and disease-free survival, particularly in biologically aggressive subtypes such as HER2-positive and triple-negative tumours. Response assessment during NAC has traditionally relied on anatomical criteria, including RECIST, and on magnetic resonance imaging (MRI), which provides detailed morphological and functional information. However, these techniques have limited ability to detect early metabolic changes or minimal residual disease. In this setting, 18F-FDG PET-CT (18F-FDG Positron Emission Tomography-Computer Tomography) has gained interest by providing functional information on tumour metabolic activity. Parameters such as SUV, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) allow a more comprehensive estimation of tumour burden and may anticipate final histopathological outcomes, supporting more accurate decision-making and potential surgical de-escalation strategies. Objectives The primary objective was to determine the predictive value of metabolic response assessed by 18F-FDG PET-CT at the end of NAC in patients with breast cancer to anticipate pathological complete response. Secondary objectives included analysing the correlation between metabolic response in the primary tumour and regional lymph nodes and final pathological findings, identifying metabolic parameters associated with response or non-response, and assessing the influence of molecular subtype on PET-CT performance. Materials and Methods A prospective observational study was conducted in patients with breast cancer scheduled for primary systemic therapy. Each patient underwent two 18F-FDG PET-CT examinations: one before treatment initiation and another after completing NAC and prior to surgery. Metabolic response was evaluated qualitatively (complete or incomplete metabolic response) and using semiquantitative parameters (SUV, MTV, and TLG). Pathological response was assessed with the Residual Cancer Burden (RCB) system. Clinical, immunohistochemical, and metabolic variables were collected. Associations between metabolic and pathological response were analysed using contingency tables and hypothesis testing, including sensitivity, specificity, predictive values, and the Kappa index. Uni- and multivariable logistic regression models were applied to identify independent predictors. Results Of the 121 patients initially assessed, 105 met inclusion criteria. The mean age was 47 years (SD ±10.8), with 64.8% being premenopausal. Overall, 37.1% achieved pCR (RCB-0), and 53.3% showed a complete metabolic response (CMR). PET-CT demonstrated a sensitivity of 92%, specificity of 70%, positive predictive value of 0.64, and negative predictive value of 0.94, with a Kappa index of 0.57 (p < 0.001). Volumetric parameters, particularly MTV in the post-treatment PET (PET2), emerged as independent predictors of complete response. Concordance between metabolic and pathological response was strongest in HER2-positive and triple-negative tumours and more limited in luminal subtypes. Conclusions Post-treatment 18F-FDG PET-CT showed high predictive capacity for anticipating pathological complete response in breast cancer. The absence of abnormal metabolic uptake was associated with high sensitivity and an excellent negative predictive value, supporting its role as a non-invasive tool to exclude residual disease. A significant correlation was observed between metabolic response and final pathology in both the primary tumour and regional lymph nodes. Among the evaluated parameters, post-NAC MTV was a consistent independent predictor of response. Predictive performance varied by molecular subtype, being higher in HER2-positive and triple-negative tumours and more limited in luminal cancers, highlighting the importance of biologically contextualised PET interpretation.
Introduction Breast cancer remains the most common malignancy among women and one of the leading causes of cancer-related mortality worldwide. The incorporation of neoadjuvant chemotherapy (NAC), also referred to as primary systemic therapy, has enabled tumour downstaging, facilitated breast-conserving surgery, and allowed direct assessment of treatment response. Achieving a pathological complete response (pCR) is associated with improved prognosis and disease-free survival, particularly in biologically aggressive subtypes such as HER2-positive and triple-negative tumours. Response assessment during NAC has traditionally relied on anatomical criteria, including RECIST, and on magnetic resonance imaging (MRI), which provides detailed morphological and functional information. However, these techniques have limited ability to detect early metabolic changes or minimal residual disease. In this setting, 18F-FDG PET-CT (18F-FDG Positron Emission Tomography-Computer Tomography) has gained interest by providing functional information on tumour metabolic activity. Parameters such as SUV, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) allow a more comprehensive estimation of tumour burden and may anticipate final histopathological outcomes, supporting more accurate decision-making and potential surgical de-escalation strategies. Objectives The primary objective was to determine the predictive value of metabolic response assessed by 18F-FDG PET-CT at the end of NAC in patients with breast cancer to anticipate pathological complete response. Secondary objectives included analysing the correlation between metabolic response in the primary tumour and regional lymph nodes and final pathological findings, identifying metabolic parameters associated with response or non-response, and assessing the influence of molecular subtype on PET-CT performance. Materials and Methods A prospective observational study was conducted in patients with breast cancer scheduled for primary systemic therapy. Each patient underwent two 18F-FDG PET-CT examinations: one before treatment initiation and another after completing NAC and prior to surgery. Metabolic response was evaluated qualitatively (complete or incomplete metabolic response) and using semiquantitative parameters (SUV, MTV, and TLG). Pathological response was assessed with the Residual Cancer Burden (RCB) system. Clinical, immunohistochemical, and metabolic variables were collected. Associations between metabolic and pathological response were analysed using contingency tables and hypothesis testing, including sensitivity, specificity, predictive values, and the Kappa index. Uni- and multivariable logistic regression models were applied to identify independent predictors. Results Of the 121 patients initially assessed, 105 met inclusion criteria. The mean age was 47 years (SD ±10.8), with 64.8% being premenopausal. Overall, 37.1% achieved pCR (RCB-0), and 53.3% showed a complete metabolic response (CMR). PET-CT demonstrated a sensitivity of 92%, specificity of 70%, positive predictive value of 0.64, and negative predictive value of 0.94, with a Kappa index of 0.57 (p < 0.001). Volumetric parameters, particularly MTV in the post-treatment PET (PET2), emerged as independent predictors of complete response. Concordance between metabolic and pathological response was strongest in HER2-positive and triple-negative tumours and more limited in luminal subtypes. Conclusions Post-treatment 18F-FDG PET-CT showed high predictive capacity for anticipating pathological complete response in breast cancer. The absence of abnormal metabolic uptake was associated with high sensitivity and an excellent negative predictive value, supporting its role as a non-invasive tool to exclude residual disease. A significant correlation was observed between metabolic response and final pathology in both the primary tumour and regional lymph nodes. Among the evaluated parameters, post-NAC MTV was a consistent independent predictor of response. Predictive performance varied by molecular subtype, being higher in HER2-positive and triple-negative tumours and more limited in luminal cancers, highlighting the importance of biologically contextualised PET interpretation.
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