RESUMEN
Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.
Asunto(s)
Neoplasias , Secuenciación Completa del Genoma , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Niño , Masculino , Preescolar , Femenino , Adolescente , Lactante , Pruebas Genéticas/métodos , Genoma Humano/genética , Genómica/métodos , Recién NacidoRESUMEN
Over the past decade, targeted therapy for oncogene-driven NSCLC and immune checkpoint inhibitors for non-oncogene-driven NSCLC, respectively, have greatly improved the survival and quality of life for patients with unresectable NSCLC. Increasingly, these biomarker-guided systemic therapies given before or after surgery have been used in patients with early-stage NSCLC. In March 2022, the US FDA granted the approval of neoadjuvant nivolumab and chemotherapy for patients with stage IB-IIIA NSCLC. Several phase II/III trials are evaluating the clinical efficacy of various neoadjuvant immune checkpoint inhibitor combinations for non-oncogene-driven NSCLC and neoadjuvant molecular targeted therapies for oncogene-driven NSCLC, respectively. However, clinical application of precision neoadjuvant treatment requires a paradigm shift in the biomarker testing and multidisciplinary collaboration at the diagnosis of early-stage NSCLC. In this comprehensive review, we summarize the current diagnosis and treatment landscape, recent advances, new challenges in biomarker testing and endpoint selections, practical considerations for a timely multidisciplinary collaboration at diagnosis, and perspectives in emerging neoadjuvant precision systemic therapy for patients with resectable, early-stage NSCLC. These biomarker-guided neoadjuvant therapies hold the promise to improve surgical and pathological outcomes, reduce systemic recurrences, guide postoperative therapy, and improve cure rates in patients with resectable NSCLC.
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Anticuerpos Biespecíficos/uso terapéutico , Leucemia Bifenotípica Aguda/tratamiento farmacológico , Neoplasia Residual/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Anciano , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/farmacología , Antígenos CD19/efectos de los fármacos , Antígenos CD19/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , N-Metiltransferasa de Histona-Lisina/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Lactante , Leucemia Bifenotípica Aguda/genética , Leucemia Bifenotípica Aguda/patología , Masculino , Proteína de la Leucemia Mieloide-Linfoide/efectos de los fármacos , Proteína de la Leucemia Mieloide-Linfoide/genética , Neoplasia Residual/genética , Neoplasia Residual/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Supervivencia sin Progresión , Inducción de Remisión , Resultado del TratamientoRESUMEN
Although outcomes for children with B-cell non-Hodgkin lymphoma are excellent, between 20% and 40% demonstrate residual radiologic abnormalities at disease assessment during consolidation therapy, the significance of which remains uncertain. The authors report the outcomes for all children treated for B-cell non-Hodgkin lymphoma at our center over an 11-year period. Twenty-four of 64 (38%) children had residual radiologic abnormalities at disease remission assessment. Seven (29%) underwent histologic biopsies that were normal. No children with residual radiologic abnormalities experienced disease relapse or death, suggesting that imaging at this time point creates clinical uncertainty without indicating residual disease or predicting relapse.
Asunto(s)
Linfoma de Células B/diagnóstico por imagen , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Imagen por Resonancia Magnética , Masculino , Neoplasia Residual/diagnóstico por imagen , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/patología , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , UltrasonografíaAsunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus/metabolismo , Infecciones por Coronavirus , Quimioterapia de Inducción , Pandemias , Neumonía Viral , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adenosina Monofosfato/administración & dosificación , Alanina/administración & dosificación , COVID-19 , Preescolar , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/etiología , Humanos , Masculino , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , SARS-CoV-2RESUMEN
OBJECTIVES: To present a structured approach to the management of a child with a mediastinal mass presenting to the emergency department. To raise awareness of presenting features of less-obvious mediastinal masses and to encourage consideration of mediastinal masses in differential diagnoses. METHODS: Review of the relevant literature and review of London Paediatric Cancer Network supportive guidelines and subsequent description of the approach to a child presenting with features suggestive of a mediastinal mass. CONCLUSIONS: A systematic approach to history taking, clinical examination and investigation of a child presenting with a mediastinal mass will assist in the safe and timely management of children presenting when they are critically unwell. Anticipation of potential management complications and early transfer for ongoing management will improve patient outcomes and minimise morbidity.
Asunto(s)
Neoplasias del Mediastino/diagnóstico , Manejo de la Vía Aérea , Diagnóstico Diferencial , Humanos , Mediastino/diagnóstico por imagen , Anamnesis , Examen FísicoAsunto(s)
Antifúngicos , Protocolos de Quimioterapia Combinada Antineoplásica , Infecciones Fúngicas Invasoras , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Antifúngicos/administración & dosificación , Antifúngicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Infecciones Fúngicas Invasoras/sangre , Infecciones Fúngicas Invasoras/inducido químicamente , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , Londres/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenAsunto(s)
Colonoscopía/efectos adversos , Embolización Terapéutica/métodos , Hemorragia Gastrointestinal/terapia , Esponja de Gelatina Absorbible/administración & dosificación , Hemorragia Posoperatoria/terapia , Enfermedades del Recto/cirugía , Várices/cirugía , Anciano , Angiografía de Substracción Digital , Embolización Terapéutica/instrumentación , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Flebografía/métodos , Hemorragia Posoperatoria/diagnóstico por imagen , Hemorragia Posoperatoria/etiología , Enfermedades del Recto/diagnóstico por imagen , Enfermedades del Recto/etiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Várices/diagnóstico por imagen , Várices/etiologíaRESUMEN
Postoperative biliary leaks have become more common in the past three decades since the development of laparoscopic biliary surgery. The role of the radiologist and interventional radiologist is important in the diagnosis and treatment of such complications, and can play an adjunctive role in the definitive surgical repair. Ultrasound, computed tomography, magnetic resonance cholangiopancreatography, nuclear medicine cholescintigraphy studies, and percutaneous transhepatic cholangiograms (PTC) are the various imaging modalities used for diagnosis. Interventional radiology treatment involves percutaneous drainage of bilomas, characterization of the biliary tree and assessment of the site of ductal injury with PTC, and biliary diversion with external biliary drainage.
Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/secundario , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Recurrencia , Adulto JovenRESUMEN
With modern cross-sectional imaging techniques, cystic lesions are very common and usually incidental findings, especially if small. However, when cysts enlarge, become infected, bleed, or undergo torsion, they can be symptomatic, and percutaneous drainage can be effective in the management. When cysts recur after aspiration, which is often the case for hepatic and renal cysts, cyst sclerosis or surgical unroofing may be required. This article describes the indications for and technical aspects of percutaneous sclerotherapy of cystic lesions of multiple organ systems.
RESUMEN
The management of complicated appendicitis in children has evolved significantly over the last century. What initially was a surgeon's dilemma is becoming the interventional radiologist's task because image-guided percutaneous drainage of abscesses from a ruptured appendix obviates the need for urgent surgery and allows for selective interval appendectomy at the surgeon's discretion (versus conservative nonoperative management in selected cases). This paradigm shift places the onus on the interventional radiologist to recognize when the procedure is emergently indicated and to be cognizant of the special needs of a pediatric patient.
RESUMEN
Given the complex embryogenesis of the inferior vena cava (IVC), anatomic variations are commonly encountered. Duplication of the IVC occurs in up to 2.8% of the population. Though asymptomatic, a duplicated IVC has important clinical implications when attempting caval filtration. We present the case of a 45- year-old male with factor V leiden and protein C deficiency, who required cessation of warfarin anticoagulation in preparation for cervical laminectomy. The patient had a duplicated IVC and required placement of a caval filter in each IVC.
Asunto(s)
Resistencia a la Proteína C Activada/terapia , Laminectomía , Deficiencia de Proteína C/terapia , Filtros de Vena Cava , Vena Cava Inferior/anomalías , Trombosis de la Vena/prevención & control , Resistencia a la Proteína C Activada/sangre , Resistencia a la Proteína C Activada/genética , Anticoagulantes/administración & dosificación , Factor V/genética , Humanos , Laminectomía/efectos adversos , Masculino , Persona de Mediana Edad , Flebografía/métodos , Deficiencia de Proteína C/sangre , Deficiencia de Proteína C/complicaciones , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Vena Cava Inferior/diagnóstico por imagen , Trombosis de la Vena/sangre , Trombosis de la Vena/etiología , Warfarina/administración & dosificaciónRESUMEN
The multiple polymorphisms contributing to Alzheimer disease (AD) have been difficult to identify. Three essentially sufficient risk sets were found using a fuzzy latent classification statistical model; that is, grade-of-membership analysis, and genotypes for APOE, APOCI, LDLr, cystatin C, and cathepsin D (180 cases, 120 controls). These were: (a) CST3:GA and CTSD:CT; (b) APOE44 and LDLr8:GG and LDLr13:TT; and (c) APOE34 and LDLr13:TC. Consonance with one of the groups and high aggregate membership carried >800-fold elevated risk for AD. The absence of these combinations defined low risk. APOE3/- with heterozygous promoter and receptor genotypes predicted long life without dementia.
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Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Catepsina D/genética , Cistatina C , Cistatinas/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Receptores de LDL/genéticaRESUMEN
INTRODUCTION: Ventriculo-peritoneal (VP) shunt malfunction is usually due to blockage of the ventricular catheter and this is typically apparent as enlarged ventricles on a CT scan of the brain. We describe a less common radiological finding in an infant with a blocked shunt. CASE REPORT: A male infant presenting with hydrocephalus in the neonatal period underwent insertion of a VP shunt. He represented at 17 months of age with the clinical features of raised intracranial pressure. A CT scan of the brain revealed that the ventricles were smaller compared with his previous scan, but X-rays taken as part of the shunt series revealed diastasis of the sagittal, coronal and lambdoid sutures. The shunt was explored and the ventricular catheter was found to be blocked and was replaced. Post-operatively there was complete resolution of the symptoms and the suture diastasis. CONCLUSIONS: Suture diastasis with small ventricles on a CT scan of the brain is an unusual radiological finding in an infant with a blocked shunt. Suture diastasis in this patient suggests raised intracranial volume and this may be due to the transependymal absorption of CSF into the white matter.
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Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Suturas Craneales/fisiopatología , Hidrocefalia/etiología , Suturas Craneales/patología , Humanos , Hidrocefalia/patología , Hidrocefalia/cirugía , Lactante , Presión Intracraneal/fisiología , Masculino , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult. METHODS: The authors used fluorescent microsatellite genotyping following laser-capture microdissection and chromosome in situ hybridization (CISH) to perform a genetic analysis of six patients with histologically diagnosed PHM who subsequently developed metastatic gestational trophoblastic neoplasia. RESULTS: Patients ranged in age from 25 years to 44 years (mean, 33.2 years). The gestational age of the molar pregnancies varied from 6 weeks to 20 weeks. All six patients had pulmonary metastases, with additional liver metastasis in two patients. Among the six patients with histologically diagnosed PHM, it was found that four patients had a diploid karyotype and no maternal alleles; thus, their neoplasms actually were CHM. Maternal genome was detected in the remaining two patients consistent with a biparental origin, and these patients had a triploid karyotype. CISH findings in all patients correlated with the genotyping findings. Triploid HM had maternally derived alleles, whereas diploid HMs were purely androgenetic. CONCLUSIONS: In the current study, which may be the largest series of genetically analyzed metastatic PHMs to date, the difficulty of histologic distinction between PHM and CHM was confirmed. Molecular analysis may help to refine the classification of HM. Although the current findings support the belief that most aggressive trophoblastic diseases are derived from CHM, a small number of PHMs do progress to metastatic disease. Thus, the current study reaffirmed that all patients with HM should be followed closely irrespective of histologic subclassification.