Summary Background Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course. Methods In this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony. Finding Between Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups. Interpretation Almost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA. Funding Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.
Integrin αvβ6 plays a key role in the fibrotic pathway by activation of Transforming Growth Factor β. Expression of αvβ6 integrin in alveolar epithelium increases after radiotherapy (RT) before onset of fibrosis and anti- αvβ6 therapy prevents fibrogenesis. Post-RT lung fibrosis, a major barrier to improved cure rate presents as progressive pulmonary injury. The utility of PET imaging with a αvβ6 integrin ligand was evaluated in patients with non-small cell lung cancer following pulmonary RT. Subjects who had received pulmonary RT within 6 months were recruited. PET imaging of the lungs over 60 minutes was performed after administration of a fluorine-18 radiolabelled 20 amino acid αvβ6-specific peptide ligand, [18F]-FBAA20FMDV2 (IMAFIB; Cancer Research Technologies (CRT) patented). PET-CT scans were co-registered with the RT planning (RTP) scans and segmented to regions corresponding to RT doses of > 40 Gy (excluding tumour), 25-40 Gy, 15-25 Gy, 8-15 Gy and < 8 Gy. Time activity curves and the standardised uptake values (SUVs) were calculated and comparisons made between RT dose and PET uptake (SUV). Linear regression between SUV and RT dose was performed for each subject and normalised to an intercept of 1. 6 subjects (3M; 3 F) aged 51-75 years underwent an IMAFIB-PET scan between 6 -22 weeks after RT completion and mean IMAFIB radioactivity of 45.4 (range 8.9 – 122) MBq administered. 5 subjects received conformal external beam RT, while one subject received stereotactic RT (SBRT). A correlation between a higher PET uptake (SUV) and higher RT doses received by the lung was observed in all subjects with a significant relationship (p < 0.05) in 3 of the 6 subjects (table). The averaged normalised SUV across all subjects increased monotonically with RT dose, between 1.05 ± 0.14 at 4 Gy and 1.58 ± 0.31 at 52 Gy. Subject No.111216172021RT dose and fractionation55Gy in 5 fractions. SBRT64 Gy in 32 fractions45 Gy in 15 fractions50 Gy in 20 fractions64 Gy in 32 fractions64 Gy in 32 fractionsTime between completion of RT and PET scan (weeks)822136714Gradient of relationship between PET uptake and RT dose0.0290.0050.0100.0060.0030.008Intercept1.3050.5040.8370.3910.6910.469r20.8410.5390.8360.8790.3100.672p value0.0280.1580.0300.0180.1630.089 A relationship between IMAFIB PET uptake and RT dose is consistent with RT dose-related activation of αvβ6 integrin in the irradiated lung and to the induction of lung fibrosis in subjects receiving pulmonary RT. Citation Format: Azeem Saleem, Yusuf Helo, Graham Searle, Fatjon Dekaj, Jo Cook, Zarni Win, Roger Gunn, Paula Wells. Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1144.
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