Variant allele fraction of genomic alterations in circulating tumor DNA (%ctDNA) correlates with SUVmax in PET scan.

The relationship between higher variant allele fraction (VAF) of genomic alterations in circulating tumor DNA (%ctDNA), an indicator of poor outcome, and maximum standardized uptake value (SUVmax), the most commonly used semi-quantitative parameter in 18F-FDG PET/CT, has not been studied. Overall, 433 cancer patients had blood-based next generation sequencing. Maximum and sum of %ctDNA alterations (%ctDNAmax and %ctDNAsum, respectively) represent the maximum and sum of VAF, reported as a percentage. The subset of 46 eligible patients had treatment-naïve metastatic disease and PET/CT imaging, with median 13 days prior to ctDNA testing. We found a linear correlation between the maximum VAF (%ctDNAmax) (as well as the sum of the VAFs (%ctDNAsum)) and SUVmax of the most 18F-FDG-avid lesion (r=0.43, P=0.003; r=0.43, P=0.002; respectively). Our data suggest that SUVmax may be a non-invasive and readily available surrogate indicator for %ctDNA, a prognostic factor for patient survival. Since higher %ctDNA has been previously correlated with worse outcome, the relationship between SUVmax, %ctDNA and survival warrants further study.

Imaging of Fibrous Dysplasia Protuberans, an Extremely Rare Exophytic Variant of Fibrous Dysplasia.

This paper details the case report of a 26-year-old man who presented with a growing right-sided skull mass evaluated with ultrasound, non-contrast CT, contrast-enhanced MRI and 99mTc-MDP whole body bone scan with SPECT/CT. These studies suggested a broad differential diagnosis favoring benign osseous lesions. Given a more recent increase in the rate of growth, headache and large size, the lesion was excised via craniotomy followed by cranioplasty. Pathology confirmed fibrous dysplasia (FD) as the diagnosis. Interestingly, this report is the imaging evaluation of the exophytic subtype of FD, the so-called FD protuberance, an extremely rare variant of FD, of which only two case reports are found in the literature.

Rosai-Dorfman-Destombes (RDD) disease presenting as palindromic rheumatism.

BACKGROUND: Rosai-Dorfman-Destombes (RDD) disease, is a rare proliferative and inflammatory disorder of non-Langerhans cell histiocytes. CASE PRESENTATION: We report a 35-year-old woman, who originally presented with recurrent episodes of lower extremity joint/bone pain and chronic nasal stuffiness and congestion. Her worsening nasal congestion was due to an obstructing nasal cavity lesion which was subsequently biopsied. Pathology was consistent with RDD. 18F-FDG PET images demonstrated intense uptake in the paranasal sinuses and a large pelvic lymph node. Focal osseous lesions with intense 18F-FDG uptake were also observed in the lower extremity, corresponding to areas of peri-articular pain. Rheumatologic work-up was consistent with palindromic rheumatism. She was diagnosed with immune-related disseminated RDD, presenting as palindromic rheumatism. CONCLUSIONS: This is the first case of RDD presenting as palindromic rheumatism. RDD should be considered as a possible but rare diagnosis in young patients with sinus-related symptoms and lymphadenopathy. The disease can on rare occasions be disseminated and can also present as immune-related RDD, such as in this patient.

Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients.

PURPOSE: Deriving links between imaging and genomic markers is an evolving field. 2-[18F]FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography-computed tomography) is commonly used for cancer imaging, with maximum standardized uptake value (SUVmax) as the main quantitative parameter. Tumor mutational burden (TMB), the quantitative variable obtained using next-generation sequencing on a tissue biopsy sample, is a putative immunotherapy response predictor. We report the relationship between TMB and SUVmax, linking these two important parameters. METHODS: In this pilot study, we analyzed 1923 patients with diverse cancers and available TMB values. Overall, 273 patients met our eligibility criteria in that they had no systemic treatment prior to imaging/biopsy, and also had 2-[18F]FDG PET/CT within 6 months prior to the tissue biopsy, to ensure acceptable temporal correlation between imaging and genomic evaluation. RESULTS: We found a linear correlation between TMB and SUVmax (p < 0.001). In the multivariate analysis, only TMB independently correlated with SUVmax, whereas age, gender, and tumor organ did not. CONCLUSION: Our observations link SUVmax in readily available, routinely used, and noninvasive 2-[18F]FDG PET/CT imaging to the TMB, which requires a tissue biopsy and time to process. Since higher TMB has been implicated as a prognostic biomarker for better outcomes after immunotherapy, further investigation will be needed to determine if SUVmax can stratify patient response to immunotherapy.

Standardized uptake value (SUVmax) in 18F-FDG PET/CT is correlated with the total number of main oncogenic anomalies in cancer patients.

Cancer diagnosis and therapy is quickly moving from the traditional histology-based approaches to genomic stratification, providing a huge opportunity for radiogenomics, associating imaging features with genomic data. Genome sequencing is time consuming, expensive and invasive whereas 18F-FDG PET/CT is readily available, fast and noninvasive. The aim of this study was to determine the relationship between the maximum standardized uptake value (SUVmax) and the frequency of 11 common oncogenic anomalies determined by specific common genomic alterations in tissue biopsies from patients with cancer. We retrospectively studied 102 consecutive untreated patients with gastrointestinal, lung, and breast cancer who underwent 18F-FDG PET/CT imaging, shortly prior to molecular testing by a biopsy for genomic profiling that consisted of 11 common DNA alterations: (1) TP53, (2) DNA repair, (3) EGFR, (4) PI3K/AKT/MTOR (PAM) pathway including PTEN, PIK3CA, AKT, TSC, CCNB1, MTOR, FBXW2, and NF2, (5) MEK, (6) CYCLIN including CCND,CDK, CDKN, and RB, (7) WNT, (8) ALK, (9) MYC, (10) MET, and (11) FGF/FGFR. Higher SUVmax was associated with the presence of TP53 and PAM genomic anomalies (p < .05), but not the other 9 gene groups (p > .05). More importantly, SUVmax was positively correlated with total number of oncogenic anomalies (r = 0.27, p = .005). We propose higher SUVmax as an indicator for total number of common oncogenic anomalies. This finding is a step forward in noninvasive stratification of cancer patients, in terms of the overall load of oncogenic anomalies, based on their SUVmax.

Single-molecule study of the CUG repeat-MBNL1 interaction and its inhibition by small molecules.

Effective drug discovery and optimization can be accelerated by techniques capable of deconvoluting the complexities often present in targeted biological systems. We report a single-molecule approach to study the binding of an alternative splicing regulator, muscleblind-like 1 protein (MBNL1), to (CUG)n = 4,6 and the effect of small molecules on this interaction. Expanded CUG repeats (CUG(exp)) are the causative agent of myotonic dystrophy type 1 by sequestering MBNL1. MBNL1 is able to bind to the (CUG)n-inhibitor complex, indicating that the inhibition is not a straightforward competitive process. A simple ligand, highly selective for CUG(exp), was used to design a new dimeric ligand that binds to (CUG)n almost 50-fold more tightly and is more effective in destabilizing MBNL1-(CUG)4. The single-molecule method and the analysis framework might be extended to the study of other biomolecular interactions.