Frequency and characteristics of pulmonary nodules in children at computed tomography

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Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring

Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors

Frequency and characteristics of pulmonary nodules in children at computed tomography

Background: Normative data on pulmonary nodules in children without malignancy are limited. Knowledge of the frequency and characteristics of pulmonary nodules in healthy children can influence care decisions in children with malignant disease. Objective: To provide normative data concerning the frequency and characteristics of pulmonary nodules on computed tomography (CT) in young children. Materials and methods: All children ages 1 year–12 years who underwent chest CT after high-energy trauma were retrospectively investigated. Exclusion criteria were a history of malignancy, thick image slices, motion artefacts and extensive post-traumatic pulmonary changes. Two radiologists were asked to independently identify all nodules and to characterize each nodule with respect to location, size, perifissural location and calcification. Discrepancies were adjudicated by a third reader, who set the reference standard in this study. Interobserver agreement in detection and characterization was assessed using the kappa coefficient (κ). Results: Identified were 120 patients, of whom 72 (75% male; median age: 8.0 years [interquartile range: 4–11]) were included. A total of 59 pulmonary nodules were present in 27 patients (38%; 95% confidence interval: 26–49%; range: 1–5 nodules per patient, with a mean diameter of 3.2 mm [standard deviation: 0.9 mm]). For nodule detection, the per-patient interobserver agreement was substantial (κ=0.78) and per-lobe agreement was moderate (κ=0.40). For characterization, there was fair to substantial agreement (κ=0.36–0.74). Conclusion: Small pulmonary nodules on chest CT are a common finding in otherwise healthy children, but detection and characterization have only moderate interobserver agreement

Nuclear Medicine Imaging in Neuroblastoma: Current Status and New Developments

Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[123I]iodobenzylguanidine ([123I]mIBG) whole-body scintigraphy, usually combined with single-photon emission computed tomography with computed tomography (SPECT-CT). Nevertheless, 10% of neuroblastomas are mIBG non-avid and [123I]mIBG imaging has relatively low spatial resolution, resulting in limited sensitivity for smaller lesions. More accurate methods to assess full disease extent are needed in order to optimize treatment strategies. Advances in nuclear medicine have led to the introduction of radiotracers compatible for positron emission tomography (PET) imaging in neuroblastoma, such as [124I]mIBG, [18F]mFBG, [18F]FDG, [68Ga]Ga-DOTA peptides, [18F]F-DOPA, and [11C]mHED. PET has multiple advantages over SPECT, including a superior resolution and whole-body tomographic range. This article reviews the use, characteristics, diagnostic accuracy, advantages, and limitations of current and new tracers for nuclear medicine imaging in neuroblastoma

Correction to: [18F]mFBG PET‑CT for detection and localisation of neuroblastoma: a prospective pilot study (European Journal of Nuclear Medicine and Molecular Imaging, (2023), 50, 4, (1146-1157), 10.1007/s00259-022-06063-6)

The article [ 18F]mFBG PET‑CT for detection and localisation of neuroblastoma: a prospective pilot study, written by Atia Samim, Thomas Blom, Alex J. Poot, Albert D. Windhorst, Marta Fiocco, Nelleke Tolboom, Arthur J. A. T. Braat, Sebastiaan L. Meyer Viol, Rob van Rooij, Max M. van Noesel, Marnix G. E. H. Lam, Godelieve A. M. Tytgat, and Bart de Keizer, was originally published Online First without Open Access. After publication in volume 50, issue 4, page 1146 - 1157 the author decided to opt for Open Choice and to make the article an Open Access publication

[18F]mFBG PET-CT for detection and localisation of neuroblastoma: a prospective pilot study

Purpose: Meta-[ 18F]fluorobenzylguanidine ([ 18F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [ 18F]mFBG PET-CT for imaging in neuroblastoma. Methods: In a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[ 123I]iodobenzylguanidine ([ 123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [ 123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [ 18F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score. Results: Twenty paired [ 123I]mIBG and [ 18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [ 18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [ 18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [ 123I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [ 18F]mFBG PET-CT. Compared to [ 123I]mIBG scanning, [ 18F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [ 18F]mFBG PET-CT compared to [ 123I]mIBG scanning. Conclusion: Results of this study demonstrate feasibility of [ 18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [ 18F]mFBG PET-CT compared to [ 123I]mIBG scanning. [ 18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma. Trial registration: Dutch Trial Register NL8152

Table_1_Case series on clinical applications of liquid biopsy in pediatric solid tumors: towards improved diagnostics and disease monitoring.docx

Background and aimsSolid tumors account for about 30% of all pediatric cancers. The diagnosis is typically based on histological and molecular analysis of a primary tumor biopsy. Liquid biopsies carry several advantages over conventional tissue biopsy. However, their use for genomic analysis and response monitoring of pediatric solid tumors is still in experimental stages and mostly performed retrospectively without direct impact on patient management. In this case series we discuss six clinical cases of children with a solid tumor for whom a liquid biopsy assay was performed and demonstrate the potential of liquid biopsy for future clinical decision making.MethodsWe performed quantitative real-time PCR (RT-qPCR), droplet digital PCR (ddPCR) or reduced representation bisulphite sequencing of cell-free DNA (cfRRBS) on liquid biopsies collected from six pediatric patients with a solid tumor treated between 2017 and 2023 at the Princess Máxima Center for Pediatric Oncology in the Netherlands. Results were used to aid in clinical decision making by contribution to establish a diagnosis, by prognostication and response to therapy monitoring.ResultsIn three patients cfRRBS helped to establish the diagnosis of a rhabdomyosarcoma, an Ewing sarcoma and a neuroblastoma (case 1-3). In two patients, liquid biopsies were used for prognostication, by MYCN ddPCR in a patient with neuroblastoma and by RT-qPCR testing rhabdomyosarcoma-specific mRNA in bone marrow of a patient with a rhabdomyosarcoma (case 4 and 5). In case 6, mRNA testing demonstrated disease progression and assisted clinical decision making.ConclusionThis case series illustrates the value of liquid biopsy. We further demonstrate and recommend the use of liquid biopsies to be used in conjunction with conventional methods for the determination of metastatic status, prognostication and monitoring of treatment response in patients with pediatric solid tumors.</p