Agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in children with cancer.

BACKGROUND: Accurate assessment of renal function is important in the care of children with cancer because renal function has implications for anti-tumor medication dosing and eligibility for clinical trials. OBJECTIVE: To characterize agreement between serum estimates of glomerular filtration rate (GFR) and a reference standard of radioisotopic GFR in a large pediatric oncology cohort. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study of children who had both radioisotopic GFR (99mTc-diethylenetriaminepentaacetic acid, or 99mTc-DTPA) and serum labs (creatinine, cystatin C) obtained <7 days apart between January 2017 and August 2019. We calculated estimated GFR from serum labs using published equations and calculated agreement using intraclass correlation coefficient (ICC) and Bland-Altman analysis with univariate regression to define predictors of agreement. RESULTS: We included 272 pairs of data. Mean patient age was (mean ± standard deviation) 7.8±5.7 years. Mean radioisotopic GFR was 112±33 mL/min/1.73 m2. Absolute agreement between radioisotopic GFR and serum estimates was only fair (ICC=0.46-0.58) with a mean difference of -26.6 to +0.12 mL/min/1.73 m2. For radioisotopic GFR measurements <60 mL/min/1.73 m2, mean differences were greater, with serum estimates overestimating GFR by a mean of 21.5-39.6 mL/min/1.73 m2. In multivariable modeling, significant predictors of agreement included age, height, acute kidney injury and tumor type. Sensitivity of serum estimates was 14-29% for a GFR <60 mL/min/1.73 m2. CONCLUSION: Agreement between radioisotopic GFR and serum estimates of GFR is only fair and serum estimates of GFR have poor sensitivity for clinically relevant GFR <60 mL/min/1.73 m2. Radioisotopic measurement of GFR likely remains necessary to assess renal function in pediatric oncology patients with decreased renal function.

Prognostic significance of pretreatment 18F-FDG positron emission tomography/computed tomography in pediatric neuroblastoma.

BACKGROUND: 18F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) shows tumor activity in most neuroblastomas, but the role of 18F-FDG PET/CT in neuroblastoma remains to be defined. OBJECTIVE: This study explored the prognostic significance of 18F-FDG PET in newly diagnosed neuroblastic tumors. MATERIALS AND METHODS: This retrospective study reviewed all 18F-FDG PET/CT examinations performed for a new diagnosis of suspected neuroblastoma. MYCN amplification status, tumor recurrence and survival were abstracted from the medical record. Primary tumors were manually segmented to measure maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), tumor volume and total lesion glycolysis. Univariate and multivariable analyses using Cox proportional hazards regression testing assessed the predictive performance of PET indices for event-free survival and overall survival with thresholds determined using receiver operating characteristic curve analysis. RESULTS: Fifty-five children were included, with a median age of 2.9 years (interquartile range [IQR] 1.8-3.0 years). SUVmax, tumor volume and total lesion glycolysis were higher in MYCN-amplified tumors (P=0.012, P<0.0001, P<0.0001, respectively) and in higher International Neuroblastoma Risk Group (INRG) stages (P=0.0008, P=0.0017, P=0.0017, respectively). After adjusting for age, tumor SUVmax (P=0.028) and SUVmean (P=0.045) were associated with overall survival. An SUVmax threshold of 4.77 (P=0.028) best predicted overall survival, with median overall survival of 2,604 days (SUVmax>4.77) vs. >2,957 days (SUVmax≤4.77). No PET parameters were independently significantly associated with overall survival or event-free survival after controlling for MYCN status, stage or treatment risk stratification. CONCLUSION: Tumor metabolic activity is higher in higher-stage MYCN-amplified neuroblastic tumors. Higher SUVmax and SUVmean were associated with worse overall survival but were not independent of other prognostic markers.

Carbofluoresceins and carborhodamines as scaffolds for high-contrast fluorogenic probes.

Fluorogenic molecules are important tools for advanced biochemical and biological experiments. The extant collection of fluorogenic probes is incomplete, however, leaving regions of the electromagnetic spectrum unutilized. Here, we synthesize green-excited fluorescent and fluorogenic analogues of the classic fluorescein and rhodamine 110 fluorophores by replacement of the xanthene oxygen with a quaternary carbon. These anthracenyl "carbofluorescein" and "carborhodamine 110" fluorophores exhibit excellent fluorescent properties and can be masked with enzyme- and photolabile groups to prepare high-contrast fluorogenic molecules useful for live cell imaging experiments and super-resolution microscopy. Our divergent approach to these red-shifted dye scaffolds will enable the preparation of numerous novel fluorogenic probes with high biological utility.