Clinical Applications of Molecular Biomarkers in Prostate Cancer.

There is clinically relevant molecular heterogeneity in prostate cancer (PCa), but this biological diversity has had only a minimal impact on clinical practice. Treatment outcomes in patients with localised PCa are often highly variable, even among patients stratified to the same risk group or disease state based on standard clinical and pathological parameters. In recent years, the development of gene panels has provided valuable data on the di erential expression of genes in patients with PCa. Nevertheless, there is an urgent need to identify and validate prognostic and predictive biomarkers that can be applied across clinical scenarios, ranging from localised disease to metastatic castration-resistant PCa. The availability of such tools would allow for precision medicine to finally reach PCa patients. In this review, we evaluate current data on molecular biomarkers for PCa, with an emphasis on the biomarkers and gene panels with the most robust evidence to support their application in routine clinical practice.post-print789 K

Iodine increases and predicts incidence of thyroiditis in NOD mice : histopathological and ultrastructural study

Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed. A potassium iodide intake of 0.2 mg/animal/day was administered via drinking water, in experimental groups of 60 and 90 days (EG60 and EG90). Distended rough endoplasmic reticulum, degenerated mitochondria, debris and amorphous spaces or ‘ill-defined’ spaces were observed with electron microscopy (EM). Lymphocyte infiltration was observed in the two groups and the time of exposure to iodine did not increase the appearance of lymphocyte infiltration but significantly associated with the development of necrosis. The results of the present study demonstrated that the NOD mouse is a feasible experimental model for thyroiditis induced by iodine administration and may represent an opportunity to analyze the steps and factors associated with genetic autoimmune thyroiditis. High doses of ingested iodine were observed to precdict and increase the incidence of the thyroiditis process

Breast radiotherapy in elderly women: myths, controversies, and current techniques in the adjuvant setting

In developed countries, breast cancer (BC) is the most common type of cancer in women, mainly affecting patients over age 60. Due to the increasing life expectancy and population ageing, the incidence of BC is expected to increase significantly in the coming years. However, no standardized clinical guidelines are available to assist in decision-making in elderly patients. Moreover, there is a lack of quality scientific evidence to guide treatment selection in this patient population, who are underrepresented in clinical trials. Consequently, up to 50% of elderly women are treated suboptimally, which implies a worse prognosis and survival. Given that the current estimated life expectancy of a healthy 70-year-old woman is 15 years, any treatment capable of reducing the likelihood of disease recurrence and cancer-specific mortality in this patient population would be beneficial. Adjuvant radiotherapy (RT) is one of the pillars of treatment for BC and it plays a key role in improving local control (LC) and overall survival (OS). Adjuvant RT is clearly indicated in young patients who undergo breast-conserving surgery (BCS) as well as in high risk patients, regardless of age. However, the use of adjuvant RT in older patients with early-stage disease has decreased in recent years—even in patients who undergo BCS—due to outdated concerns about the possible side effects of RT and reports suggesting that RT can be omitted in low-risk patients. One of the greatest challenges currently facing radiation oncologists who specialise in the treatment of BC is the selection of elderly patients who are likely to benefit from adjuvant RT. There is also a clear need to critically evaluate the available evidence and to apply those findings to routine clinical practice. Given this context, the aim of the present review is to clarify the current role of adjuvant RT in the management of BC in older women—particularly those with early-stage disease—and to dispel the myths surrounding the use of RT to treat elderly women. This review primarily focuses on the indications, controversies, and irradiation techniques used in this patient subgroup.Sin financiación1.241 JCR (2020) Q4, 233/242 Oncology0.254 SJR (2020) Q4, 183/211 Cancer ResearchNo data IDR 2020UE

Breast cancer radiotherapy: What physicians need to know in the era of the precision medicine

Abstract: Breast cancer is the most common cancer in women worldwide and encompasses a broad spectrum of diseases in one with significant epidemiological, clinical, and biological heterogeneity, which determines a different natural history and prognostic profile. Although classical tumour staging (TNM) still provides valuable information, the current reality is that the clinicians must consider other biological and molecular factors that directly influence treatment decision-making. The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. This knowledge has brought with it a major impact regarding surgical and systemic management and has been practice-changing, but it has also created significant uncertainties regarding how best integrate the radiotherapy treatment into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualised treatment approaches. In this context, “precision medicine” seeks to provide an answer to these open questions and uncertainties. The aim of the present review is to clarify the meaning of this term and to critically evaluate its role and impact on contemporary breast cancer radiotherapy.Sin financiaciónNo data JCR 20200.244 SJR (2020) Q4, 185/211 Cancer ResearchNo data IDR 2020UE

Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know

External beam radiotherapy (EBRT) is one of the principal curative treatments for patients with prostate cancer (PCa). Risk group classification is based on prostate-specific antigen (PSA) level, Gleason score, and T-stage. After risk group determination, the treatment volume and dose are defined and androgen deprivation therapy is prescribed, if appropriate. Traditionally, imaging has played only a minor role in T-staging due to the low diagnostic accuracy of conventional imaging strategies such as transrectal ultrasound, computed tomography, and morphologic magnetic resonance imaging (MRI). As a result, a notable percentage of tumours are understaged, leading to inappropriate and imprecise EBRT. The development of multiparametric MRI (mpMRI), an imaging technique that combines morphologic studies with functional diffusion-weighted sequences and dynamic contrast-enhanced imaging, has revolutionized the diagnosis and management of PCa. As a result, mpMRI is now used in staging PCa prior to EBRT, with possible implications for both risk group classification and treatment decision-making for EBRT. mpMRI is also being used in salvage radiotherapy (SRT), the treatment of choice for patients who develop biochemical recurrence after radical prostatectomy. In the clinical context of biochemical relapse, it is essential to accurately determine the site of recurrence - pelvic (local, nodal, or bone) or distant - in order to select the optimal therapeutic management approach. Studies have demonstrated the value of mpMRI in detecting local recurrences - even in patients with low PSA levels (0.3-0.5 ng/mL) - and in diagnosing bone and nodal metastasis. The main objective of this review is to update the role of mpMRI prior to radical EBRT or SRT. We also consider future directions for the use and development of MRI in the field of radiation oncology.Sin financiaciónNo data JCR 20171.358 SJR (2017) Q1, 91/378 OncologyNo data IDR 2017UE

Role of 3T multiparametric magnetic resonance imaging without endorectal coil in the detection of local recurrent prostate cancer after radical prostatectomy: the radiation oncology point of view

The aims of this study were to evaluate the role of 3 tesla multiparametric magnetic resonance imaging (3TmMRI) without endorectal coil in the detection of radiographic local recurrences (rLRs) in a contemporary cohort of patients with prostate cancer who presented with biochemical recurrence after radical prostatectomy (RP) with low prostate-specific antigen (PSA) levels, and to identify clinical parameters associated with the 3TmMRI findings.Sin financiación1.346 JCR (2015) Q3, 53/77 Urology & nephrologyUE

Breast Radiotherapy-Related Cardiotoxicity. When, How, Why. Risk Prevention and Control Strategies

In recent decades, improvements in breast cancer management have increased overall patient survival; however, many cancer therapies have been linked to an important risk of cardiovascular adverse events. Cardio-oncology has been proposed as an emerging specialty to coordinate preventive strategies that improve the cardiovascular health of oncologic patients. It employs the most suitable personalized multidisciplinary management approach for each patient to optimize their cardiovascular health and improve their survival and quality of life. Radiotherapy is an essential part of the therapeutic regimen in breast cancer patients but can also increase the risk of cardiovascular disease. Therefore, minimizing the negative impact of radiation therapy is an important challenge for radiotherapy oncologists and cardiologists specializing in this field. The aim of the present review is to update our knowledge about radiation-induced cardiotoxicity in breast cancer patients by undertaking a critical review of the relevant literature to determine risk prevention and control strategies currently available.Sin financiación6.639 JCR (2020) Q1, 51/242 Oncology1.349 SJR (2021) Q1, 72/369 OncologyNo data IDR 2020UE

Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with negative axillary involvement at initial diagnosis

Objetivo: valorar la tasa de detección de ganglio centinela tras quimioterapia neoadyuvante en pacientes con cáncer infiltrante de mama y axila clínicamente negativa previa al tratamiento y analizar su supervivencia global y supervivencia libre de enfermedad. Material y métodos: estudio observacional retrospectivo. Se incluyeron las pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante en el Hospital Universitario Quironsalud Madrid entre los años 2008-2014. A todas se les practicó cirugía conservadora o radical junto con biopsia selectiva de ganglio centinela posneoadyuvancia. Se recogió información correspondiente a características sociodemográficas, variables relacionadas con el tratamiento quirúrgico y médico, evolución, características del tumor, supervivencia global y supervivencia libre de enfermedad. Resultados: se incluyeron en el estudio 112 pacientes (116 tumores, 4 de ellos bilaterales). De los 112 tumores unilaterales, 98 (84,5%) estaban en estadios iniciales. La mediana de tamaño tumoral fue 20 mm (15-30). La práctica totalidad (97,4%) eran carcinomas ductales infiltrantes. La quimioterapia se basó en antraciclinas y taxanos con adición de carboplatino en los casos triple negativo y de trastuzumab en Her-2/neu sobreexpresado. Se realizó cirugía conservadora en el 59,5%. La tasa de detección de ganglio centinela fue del 100% con un valor predictivo negativo del 99,1% (110/111), al encontrar una sola recidiva axilar en los 111 ganglios centinela negativos, y se obtuvo respuesta completa patológica en el 52,6%, mayoritariamente en los tumores Her-2 puros y triples negativos con diferencia estadísticamente significativa (p:0.018). La supervivencia global fue del 99,1% con mediana de seguimiento de 53 meses, observando eventos de recaída en 10 pacientes de las cuales solo 2 fueron axilares. Conclusiones: en nuestra experiencia, la biopsia selectiva de ganglio centinela sistemática posneoadyuvancia en pacientes con axila negativa al inicio presenta una excelente tasa de detección, sin aumentar el número de recidivas axilares de forma significativa ni la supervivencia global de estas pacientes. Consideramos, por tanto, esta estrategia la mejor opción para la estadificación quirúrgica de estos tumores.Objective: To assess sentinel lymph node biopsy rate after neoadjuvant chemotherapy in breast cancer patients with negative axillary nodes at diagnosis and to analize their disease free interval and overall survival. Material and methods: Retrospective observational study including breast cancer patients with neoadjuvant chemotherapy at the Hospital Universitario Quironsalud Madrid between 2008-2014. Post chemotherapy, all patients underwent conservative or radical surgery along with a systematic sentinel lymph node biopsy. Patients data was collected and included sociodemographic characteristics, variables regarding surgical and medical treatment, follow-up, tumor characteristics, overall and disease-free survival. Results: The study included 112 patients (116 tumors, 4 of them bilateral). Of the 112 unilateral tumors, 98 (84.5%) were early stages. The median tumor size was 20 mm (15-30) and the majority (97,4%) were invasive ductal carcinoma chemotherapy was based on anthracyclines and taxanes with addition of carboplatin in triple negative cases and trastuzumab in Her-2/neu positive tumors. Conservative procedures were performed in 59,5% of cases. Sentinel lymph node detection rate reached 100% with a negative predictive value of 99,1% (110/111) finding only one axillary recurrence among 111 SLNB. We achieved pathological complete response in 52,6% of tumors in the breast, and more specifically in pure Her2/neu positive and triple negative surrogates (p:0.018). Overall survival was 99,1% with median follow-up of 53 months and 10 patients had a relapse, with only two patients with axillary involvement. Conclusions: In our experience, sentinel lymph node biopsy performed systematically after neoadjuvant treatment in clinically node negative patients have an excellent detection rate without increasing the axillary recurrence rate nor decreasing overall survival in this group of patients. We consider this strategy the best option for the surgical staging of this tumors after chemotherapy.Sin financiaciónNo data JCR 20190.123 SJR (2019) Q4, 152/185 Obstetrics and GynecologyNo data IDR 2019UE

PET/TC con 68Ga-PSMA, importancia en la práctica hospitalaria. Visión del oncólogo radioterápico

Radiotherapy is a treatment with curative intent, both in patients with primary diagnosis of prostate cancer (PCa) and in patients presenting with biochemical recurrence after radical prostatectomy (RP). Moreover, the use of stereotactic body radiotherapy as a metastasis directed therapy in patients with oligometastatic PCa has significantly increased in the recent years. Conventional imaging techniques, including transrectal ultrasound, computed tomography (CT), morphologic magnetic resonance and bone scintigraphy have traditionally played a minor role in all those clinical scenarios due to its low diagnostic accuracy. The recent development of the positron emission tomography (PET) radiotracer 68Ga-PSMA binding to the prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in PCa cells, has shown promising results. Detection rates for PCa lesions are higher than CT and higher than the best technique available, the PET/CT with choline. Its superiority has been demonstrated even at very low PSA levels (<1 ng/ml). This increase in diagnostic accuracy represents a potential impact on patient management, especially in radiotherapy. Even if this imaging technique is already available for routine clinical practice in some European countries, in Spain, unfortunately, there is very limited access. In this review, we analyze the main studies that investigate the usefulness of 68Ga-PSMA PET/CT in patients with PCa and its potential impact on radiotherapy treatments. In addition, we compared the 68Ga-PSMA PET/CT, with the multiparametric magnetic resonance imaging and the PET/CT with choline, in the different clinical scenarios.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

PET/TC con 68Ga-PSMA, importancia en la práctica hospitalaria. Visión del oncólogo radioterápico

Radiotherapy is a treatment with curative intent, both in patients with primary diagnosis of prostate cancer (PCa) and in patients presenting with biochemical recurrence after radical prostatectomy (RP). Moreover, the use of stereotactic body radiotherapy as a metastasis directed therapy in patients with oligometastatic PCa has significantly increased in the recent years. Conventional imaging techniques, including transrectal ultrasound, computed tomography (CT), morphologic magnetic resonance and bone scintigraphy have traditionally played a minor role in all those clinical scenarios due to its low diagnostic accuracy. The recent development of the positron emission tomography (PET) radiotracer 68Ga-PSMA binding to the prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in PCa cells, has shown promising results. Detection rates for PCa lesions are higher than CT and higher than the best technique available, the PET/CT with choline. Its superiority has been demonstrated even at very low PSA levels (<1 ng/ml). This increase in diagnostic accuracy represents a potential impact on patient management, especially in radiotherapy. Even if this imaging technique is already available for routine clinical practice in some European countries, in Spain, unfortunately, there is very limited access. In this review, we analyze the main studies that investigate the usefulness of 68Ga-PSMA PET/CT in patients with PCa and its potential impact on radiotherapy treatments. In addition, we compared the 68Ga-PSMA PET/CT, with the multiparametric magnetic resonance imaging and the PET/CT with choline, in the different clinical scenarios.La radioterapia es un tratamiento curativo indicado en pacientes con cáncer de próstata (CaP) primario y en aquellos con recurrencia bioquímica tras prostatectomía radical (PR). Además, recientemente, ha habido un aumento en el uso de técnicas de alta precisión como la radioterapia estereotáctica fraccionada corporal para tratar un número limitado de metástasis en pacientes con CaP oligometastásico. Las pruebas de imagen convencional (ecografía transrectal, tomografía computarizada [TC], resonancia magnética morfológica y gammagrafía ósea) tienen un papel menor en estos escenarios, debido a su bajo rendimiento diagnóstico. Recientemente, se ha desarrollado el radiotrazador 68Ga-PSMA, para la tomografía por emisión de positrones (PET), que es un ligando del antígeno de membrana específico de próstata (PSMA), una proteína transmembrana sobrexpresada en las células del CaP. Sus resultados son prometedores, con tasas de detección de lesiones tumorales mayores que la TC y mayor que la mejor técnica disponible actualmente, la PET con colina. Su superioridad es más evidente en pacientes con valores bajos de PSA (< 1 ng/ml). Esta mejora en el rendimiento diagnóstico representa un potencial impacto en el manejo terapéutico, especialmente en radioterapia. A pesar de que la prueba ya está disponible en la práctica clínica diaria de otros países europeos, en España su uso es muy limitado. En esta revisión, analizamos los principales estudios que investigan la utilidad de la PET/TC con 68Ga-PSMA en pacientes con CaP y su potencial impacto en los tratamientos de radioterapia. Además, comparamos la PET/TC con PSMA, con la resonancia magnética multiparamétrica y la PET/TC con colina, en los distintos escenarios clínicos.Sin financiaciónNo data JCR 20180.235 SJR (2018) Q3, 236/341 Radiology, Nuclear Medicine and ImagingNo data IDR 2018UE