Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18 Ffluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18 F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18 Ffluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP ($50% viable tumor), mixed TP (,50% and .10% viable tumor), or pseudoprogression (#10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40-to 50-min SUV max (6.64 1 1.88 vs. 4.11 6 1.52, P 5 0.009) than patients with pseudoprogression. A 40-to 50-min SUV max cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40to 50-min SUV max cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18 F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18 F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18 F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.
Background: Spring-mediated cranioplasty (SMC) is an increasingly utilized technique to treat patients with nonsyndromic sagittal craniosynostosis, but variables impacting outcomes are incompletely understood. The purpose of this study was to determine variables most predictive of outcomes following SMC, primarily changes in cephalic index (CI). Methods: Patients with nonsyndromic sagittal craniosynostosis undergoing SMC at our institution between 2014 and 2021 were included. Cephalic index was measured from patient computed tomography scans, x-rays, or by caliper-based methods. Parietal bone thickness was determined from patient preoperative computed tomography. Stepwise multiple regression analysis, least absolute shrinkage and selection operator, and random forest machine learning methods were used to determine variables most predictive of changes in CI. Results: One hundred twenty-four patients were included.Stepwise multiple regression analysis identified duration of spring placement (P = 0.007), anterior spring force (P = 0.034), and anterior spring length (P = 0.043) as statistically significant predictors for changes in CI. Least absolute shrinkage and selection operator analysis identified maximum spring force (β = 0.035), anterior spring length (β = 0.005), posterior spring length (β = 0.004), and duration of spring placement (β = 0.0008) as the most predictive variables for changes in CI. Random forest machine learning identified variables with greatest increase in mean squared error as maximum spring force (0.0101), anterior spring length (0.0090), and posterior spring length (0.0056). Conclusions: Maximum and total spring forces, anterior and posterior spring lengths, and duration of spring placement were the most predictive variables for changes in CI following SMC. Age at surgery and other demographic variables were inferior predictors in these models.
Objective: Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non-small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first-line ICIs ± chemotherapy remain unclear. Methods: A total of 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment were retrospectively collected from 19 locally advanced or metastatic NSCLC patients. The circulating tumor DNA (ctDNA) burden by tumor-informed assay was detected to monitor and predict the therapeutic response and survival of NSCLC patients treated with first-line ICIs or plus chemotherapy.Results: We found that ctDNA was only positively detected in one patient by tumor-agnostic assay with a mean variant allele fraction (VAF) of 6.40%, whereas it was positively detected in three patients by tumor-informed assay with a mean VAF of 8.83%, 0.154%, and 0.176%, respectively. Tumor-informed assays could sensitively detect ctDNA in 93.75% (15/16) of patients. Trends in the level of ctDNA from baseline to first evaluation was consistent with the radiographic changes. There was a greater decrease in ctDNA after treatment compared with baseline in patients with partial response compared to patients with stable disease/progressive disease. Patients with over a 50% reduction in ctDNA had a significant progression-free survival and overall survival benefit. Conclusion:The tumor-informed assay was favorable for ctDNA detection, and early dynamic changes in plasma ctDNA may be a valuable biomarker for monitoring the efficacy and predicting the outcome in advanced NSCLC patients treated with first-line ICIs ± chemotherapy.
PURPOSE Differentiation of tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in post-treatment glioblastoma (GBM). 18F-Fluciclovine is a synthetic amino acid PET radiotracer with higher uptake in tumor tissue vs. areas of treatment-related change. We investigated the value of 18F-Fluciclovine PET for differentiating PsP from TP independent from and in combination with multi-parametric MRI. METHODS We prospectively enrolled 30 patients with GBM with a new or enlarging contrast-enhancing lesion on MRI after chemoradiotherapy who were planned for surgical resection of the lesion. Patients underwent pre-operative 18F-Fluciclovine PET and multi-parametric MRI. Following surgery, the relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified. Patients were categorized as TP if viable tumor represented ≥ 50% of the specimen, mixed TP if < 50% and > 10%, and PsP if ≤ 10%. RESULTS 18 patients had TP, 4 had mixed TP, and 8 PsP. Patients with TP/mixed TP had a significantly higher 40-50 minutes SUVmax (6.64 + 1.88 vs 4.11± 1.52, p=0.009) and an SUVmax cut-off of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from PsP (AUC=0.856). A maximum cerebral blood volume (CBVmax) cut-off of 3.67 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from PsP (AUC=0.779). Combining a 40-50 minutes SUVmax cut-off of 4.662 and a relative CBVmax cut-off of 3.67 provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from PsP (AUC=0.95). The time activity curve patterns and time to peaks were not different between the groups. Normalization of PET parameters to normal brain parenchyma were not helpful to differentiate the groups due to variability in radiotracer uptake in normal brain between subjects. CONCLUSION 18F-Fluciclovine PET uptake can accurately differentiate PsP from TP in GBM patients, with even more accurate differentiation achieved when combined with MRI.
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