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Objective: Image-guided sternal biopsy may be technically daunting given the immediately subjacent critical structures. There is a paucity of literature describing technique, safety, and efficacy. This study aims to quantify the diagnostic yield and safety of image-guided sternal biopsies. Secondary aims include (1) describing the preferred approach/technique and (2) identifying imaging features and disease entities associated with higher and lower diagnostic yields., Materials and Methods: A retrospective review of 50 image-guided sternal biopsies performed at two quaternary care centers from 2000 to 2019 was performed. Recorded lesion-related variables included as follows: location, density, extraosseous extension, and size. Recorded variables from electronic medical records included as follows: patient demographics, histologic or microbiological diagnosis, and complications. Recorded technique-related variables included as follows: needle obliquity, type, and gauge; biopsy core number and length; and modality., Results: Of the 50 biopsies, 88.0% resulted in a definitive histologic diagnosis. Six biopsies were non-diagnostic. The majority of biopsies were performed under computed tomography (88.0%), followed by ultrasound (12.0%). Tumor was the most common biopsy indication (90.0%), followed by infection (10.0%). Of the diagnostic biopsies indicated for tumor, 88.9% were malignant. Seventy-four percent of the lesions were predominantly lytic. Fifty percent of lesions had extraosseous extension. Lesion locations were as follows: manubrium (48.0%), sternal body (48.0%), and sternomanubrial joint (4.0%). No minor or major, acute, or delayed procedure-related complications were encountered., Conclusion: Image-guided sternal biopsy is an efficacious and safe method of obtaining a definitive histologic diagnosis regardless of lesion-specific features or location.

Management of soft-tissue and bone neoplasms depends on a definitive histologic diagnosis. Percutaneous image-guided biopsy of bone and soft-tissue tumors is a cost-effective and accurate method to obtain a histopathologic diagnosis. Biopsy requests must be approached thoughtfully to avoid numerous potential pitfalls. Hasty biopsy planning places the patient at increased risk for misdiagnosis, delayed therapy, repeated invasive procedures, and substantial morbidity. Biopsy planning begins with a thorough review of the relevant clinical history and pertinent imaging. The biopsy route must be planned in concert with the referring orthopedic oncologist to preserve limb-sparing options. Carefully selecting the most appropriate imaging modality to guide the biopsy increases the chances of reaching a definitive diagnosis. It is also critical to identify and target with expertise the part of the lesion that is most likely to yield an accurate diagnosis. Percutaneous biopsy is a safe procedure, and familiarity with preprocedural laboratory testing parameters, anticoagulation guidelines, and commonly used sedation medications minimizes the risk of complications while ensuring patient comfort. Nondiagnostic biopsy results are not infrequent and may still have value in guiding patient treatment. Awareness of the imaging manifestations of tumor recurrence is also important. The aim of this article is to provide a comprehensive review of pertinent preprocedural, periprocedural, and postprocedural considerations for bone and soft-tissue musculoskeletal biopsies. The online slide presentation from the RSNA Annual Meeting is available for this article. © RSNA, 2020.

Background: In order to establish the workflows required to implement a real-time process involving multi-omic analysis of patient samples to support precision-guided therapeutic intervention, a tissue acquisition and analysis trial was implemented. This report describes our findings to date, including the frequency with which mutational testing led to precision-guided therapy and outcome for those patients., Methods: Eligible patients presenting to Oregon Health and Science University Knight Cancer Institute were enrolled on the study. Patients with biopsy proven metastatic or locally advanced unresectable prostate cancer, breast cancer, pancreatic adenocarcinoma, or refractory acute myelogenous leukemia receiving standard of care therapy were eligible. Metastatic site biopsies were collected and analyzed using the Knight Diagnostic Lab GeneTrails comprehensive solid tumor panel (124 genes). CLIA certified genomic information was made available to the treating physician., Results: Between 1/26/2017 and 5/30/2018, 38 patients were enrolled, with 28 successfully undergoing biopsy. Of these, 25 samples yielded sufficient tumor for analysis. The median biopsy cellularity and number of cores collected were 70% (15-90%) and 5 (2-20), respectively. No procedure-related complications occurred. GeneTrails analysis revealed that 22 of 25 (88%) tumor samples harbored at least one potentially actionable mutation, and 18 (72%) samples harbored 2 or more potentially actionable mutations. The most common genetic alterations identified involved: DNA damage repair genes, cell cycle regulating genes, PIK3CA/Akt/mTOR pathway, and FGF gene family. To date, CLIA certified genomic results were used by treating physicians for precision-guided therapy in 5 (23%) patients., Conclusion: We report the feasibility of real-time tissue acquisition and analysis to support a successful translational oncology platform. The workflow will provide the foundation to improve access and accrual to biomarker driven precision oncology trials.

This study aims to assess the utility of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters in comparison with imaging tumor size for early prediction and evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy. In total, 20 patients with intermediate- to high-grade soft tissue sarcomas received either a phase I trial regimen of sorafenib + chemoradiotherapy (n = 8) or chemoradiotherapy only (n = 12), and underwent DCE-MRI at baseline, after 2 weeks of treatment with sorafenib or after the first chemotherapy cycle, and after therapy completion. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed using the Shutter-Speed model. After only 2 weeks of treatment with sorafenib or after 1 chemotherapy cycle, K trans (rate constant for plasma/interstitium contrast agent transfer) and its percent change were good early predictors of optimal versus suboptimal pathological response with univariate logistic regression C statistics values of 0.90 and 0.80, respectively, whereas RECIST LD percent change was only a fair predictor (C = 0.72). Post-therapy K trans , v e (extravascular and extracellular volume fraction), and k ep (intravasation rate constant), not RECIST LD, were excellent (C > 0.90) markers of therapy response. Several DCE-MRI parameters before, during, and after therapy showed significant ( P < .05) correlations with percent necrosis of resected tumor specimens. In conclusion, absolute values and percent changes of quantitative DCE-MRI parameters provide better early prediction and evaluation of the pathological response of soft tissue sarcoma to preoperative chemoradiotherapy than the conventional measurement of imaging tumor size change., Competing Interests: Oregon Health & Science University and Dr. Wei Huang have a significant financial interest in Imbio, LLC., a company that may have a commercial interest in the results of this research and the Shutter-Speed technology. This potential individual and institutional conflict of interest has been reviewed and managed by Oregon Health & Science University.

Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment., Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses., Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3-4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔK(trans) after 2 weeks of sorafenib correlated with histologic response (R(2) = 0.67, P = 0.012) at surgery., Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma., (©2013 AACR.)

Background: During the last decade, there has been a movement in the United States toward utilizing size-appropriate radiation doses for pediatric body CT, with smaller doses given to smaller patients., Objective: This study assesses community adoption of size-appropriate pediatric CT techniques. Size-specific dose estimates (SSDE) in pediatric body scans are compared between community facilities and a university children's hospital that tailors CT protocols to patient size as advocated by Image Gently., Materials and Methods: We compared 164 pediatric body scans done at community facilities (group X) with 466 children's hospital scans. Children's hospital scans were divided into two groups: A, 250 performed with established pediatric weight-based protocols and filtered back projection; B, 216 performed with addition of iterative reconstruction technique and a 60% reduction in volume CT dose index (CTDIvol). SSDE was calculated and differences among groups were compared by regression analysis., Results: Mean SSDE was 1.6 and 3.9 times higher in group X than in groups A and B and 2.5 times higher for group A than group B. A model adjusting for confounders confirmed significant differences between group pairs., Conclusions: Regional community hospitals and imaging centers have not universally adopted child-sized pediatric CT practices. More education and accountability may be necessary to achieve widespread implementation. Since even lower radiation doses are possible with iterative reconstruction technique than with filtered back projection alone, further exploration of the former is encouraged.

We have cloned a mouse cDNA homolog of P450RAI, a cytochrome P450 belonging to a new family (CYP26), which has previously been isolated from zebrafish and human cDNAs and found to encode a retinoic acid-inducible retinoic acid hydroxylase activity. The cross-species conservation of the amino acid sequence is high, particularly between the mouse and the human enzymes, in which it is over 90%. Like its human and zibrafish counterparts, the mouse P450RAI cDNA catalyzes metabolism of retinoic acid into 4-OH-retinoic acid, 4-oxo-retinoic acid, 18-OH-retinoic acid, and unidentified water-soluble metabolites when transfected into COS-1 cells. Retinoic acid-inducible retinoic acid metabolism has previously been observed in F9 murine embryonal carcinoma cells and some derivatives lacking retinoid receptors. We were interested in determining whether P450RAI could be responsible for retinoic acid metabolism in F9 cells and in studying the effect of retinoid receptor ablation on P450RAI expression. In wild-type F9 cells and derivatives lacking RAR gamma, RAR alpha, and/or RXR alpha, we observed a direct relationship between the level of retinoic acid metabolic activity and retinoic acid-induced P450RAI mRNA. These experiments, as well as others using synthetic receptor subtype-specific retinoids, suggest that the RAR gamma and RXR alpha receptors mediate the effects of retinoic acid on the expression of the P450RAI gene.