Radioterapia adapatada al riesgo determinado por test de expresión genética múltiple en estadios iniciales de cáncer de mama y su impacto en el tratamiento adyuvante

INTRODUCCIÓN: El cáncer de mama (CM) estadio inicial representa aproximadamente la mitad de las enfermas con receptores hormonales (RH) positivos y sin invasión o con mínima afectación ganglionar locorregional al diagnóstico. El tratamiento adyuvante en estas pacientes se basa en la administración secuencial de radioterapia (RT) adyuvante, quimioterapia (QT) y hormonoterapia o terapia hormonal exclusiva (HT). Numerosos estudios prospectivos han demostrado que la incorporación de los test genómicos a la práctica clínica habitual tiene un impacto significativo en la decisión del tratamiento adyuvante del CM, sin embargo no existe la misma evidencia para los tratamientos locorregionales con radiación. El objetivo de los nomogramas es estratificar a los pacientes atendiendo a su riesgo para así poder individualizar los tratamientos. HIPÓTESIS Y OBJETIVOS: El objetivo principal de este estudio es identificar los parámetros que permitan categorizar con mayor precisión a los pacientes en grupos de riesgo, mediante la estratificación con una puntuación de menor a mayor riesgo de las variables clínicas, anatomopatológicas, genéticas y comorbilidad asociada, con el fin de obtener una herramienta de clasificación del riesgo de recidiva. MATERIAL Y MÉTODOS: Se ha procedido a una valoración retrospectiva de variables de riesgo. Nuestra población de interés son pacientes diagnosticadas de cáncer de mama en estadio inicial (I y II), adscritas a los departamentos de Salud Pública de la Comunidad Valenciana (C.V.), con el test genómico realizado y un seguimiento oncológico recogido en las historias clínicas. Para alcanzar el objetivo primario del estudio se han categorizado las variables de riesgo clínico-anatomo-patológico y génico. Se han ponderado dichas variables atendiendo al mayor o menor riesgo de recaída con una puntuación mínima de 1 a máxima de 5. RESULTADOS: El periodo medio de seguimiento de los pacientes ha sido de 63,2 meses (DT 9,1) con rango de 17 a 96 meses. La supervivencia libre de progresión locorregional (SLP-L) actual ha sido del 98,4%. Se han detectado 7 recaídas locorregionales y la supervivencia global actual del98,7% con cuatro fallecimientos. No se objetivaron diferencias atendiendo al tratamiento recibido ni test genómico realizado en la SLP-L ni en la SG. Se ha creado una nueva variable suma de factores clínico-patológicos, moleculares y genéticos, con el siguiente acrónimo CLINGEN y un nomograma web. CONCLUSIONES:Es una herramienta novedosa que integra los parámetros clínico-patológicos, moleculares y genéticos. Disponible on line y de fácil uso que permite inferir decisiones con cierta agilidad y rapidez. Se precisa de un seguimiento más prolongado a la espera de un mayor número de eventos para poder implementar su uso en la práctica asistencial.INTRODUCTION: Approximately half of the patients with early-stage breast cancer (BC) present disease which is positive for hormone receptors (HRs) and with no infiltrations or minimal locoregional lymph node involvement at the time of diagnosis. Adjuvant treatment in these patients is based on the sequential administration of adjuvant radiotherapy (RT), chemotherapy (CT), and hormonal therapy (HT) or the exclusive use of HT. Numerous prospective studies have shown that the incorporation of genomic tests into routine clinical practice significantly impacts decisions about adjuvant treatments for BC. However, no studies have searched for similar evidence for the decision to use locoregional radiation treatments. Nomograms are used to stratify patients according to their risk so that their treatments can be appropriately individualized. HYPOTHESIS AND OBJECTIVES: The main objective of this study was to identify the parameters that could be used to categorize patients more accurately into different risk groups, by stratifying them with a score from lowest to highest risk of clinical, pathological, genetic, and associated comorbidity variables, and thereby to obtain a recurrencerisk-classification tool. MATERIAL AND METHODS: We carried out a retrospective assessment of BC patient risk variables. Our population of interest was patients diagnosed with early stage (stages I and II) BC, assigned to public health departments in the Valencian Community, for which a genomic test had been performed and oncological follow-ups had been recorded in their medical records. To achieve the primary objective of this study, we categorized the clinical anatomopathological and genetic risk variables of these patients. We weighted these variables from a minimum score of 1 to a maximum of 5 to represent the highest to lowest risk of relapse. RESULTS: The mean patient follow-up time was 63.2 months (SD = 9.1), with a range of 17 to 96 months. To date, the locoregional progression-free survival (L-PFS) for these patients is 98.4%. Seven locoregional relapses were detected and the current overall survival of the cohort is 98.7%, with four deaths. No differences were observed in terms of the L-PFS or OS according to the treatment received or genomic test they had undergone. We created a new sum variable comprising clinicopathological and molecular genetic factors, which we named with the portmanteau ‘CLINGEN’, as well as an accompanying internet-based nomogram. CONCLUSIONS: CLINGEN is a novel tool available online that integrates clinical pathological, molecular, and genetic parameters. It is easy to use and helps physicians to infer clinical decisions with relative agility and speed. Before this tool can be used in healthcare practice, studies with longer follow-ups which will allow sufficient time for more clinical events to occur will first be required

OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial

Background: Conservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes. However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the One-Step Nucleic Acid Amplification (OSNA) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN. Methods: BC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250-15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates. Discussion: Standardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy

The Impact of Frailty Screening on Radiation Treatment Modification

Background: Care overburden makes it difficult to perform comprehensive geriatric assessments (CGAs) in oncology settings. We analyzed if screening tools modified radiotherapy in oncogeriatric patients. Methods: Patients ≥ 65 years, irradiated between December 2020 and March 2021 at the Hospital Provincial de Castellón, completed the frailty G8 and estimated survival Charlson questionnaires. The cohort was stratified between G8 score ≤ 14 (fragile) or >14 (robust); the cutoff point for the Charlson index was established at five. Results: Of 161 patients; 69.4% were male, the median age was 75 years (range 65–91), and the prevailing performance status (PS) was 0–1 (83.1%). Overall, 28.7% of the cohort were frail based on G8 scores, while the estimated survival at 10 years was 2.25% based on the Charlson test. The treatment administered changed up to 21% after frailty analysis. The therapies prescribed were 5.8 times more likely to be modified in frail patients based on the G8 test. In addition, patients ≥ 85 years (p = 0.01), a PS ≥ 2 (p = 0.008), and limited mobility (p = 0.024) were also associated with a potential change. Conclusions: CGAs remain the optimal assessment tool in oncogeriatry. However, we found that the G8 fragility screening test, which is easier to integrate into patient consultations, is a reliable and efficient aid to rapid decision making