Intraosseous Spindle Cell Rhabdomyosarcoma with MEIS1::NCOA2 Fusion - Case Report with Substantial Clinical Follow-up and Review of the Literature.

Spindle cell/sclerosing rhabdomyosarcoma (SSRMS) is a clinicopathologically and molecularly heterogeneous disease. Gene fusions have been identified in intraosseous SSRMS, consisting predominantly of EWSR1/FUS::TFCP2 and MEIS1::NCOA2. The former often follow an aggressive clinical course; there is limited clinical follow-up available for the latter. We report here a new case of the very rare intraosseous SSRMS with MEIS1::NCOA2 gene fusion and include the detailed treatment course and 52 months of clinical follow-up. SSRMS with MEIS1::NCOA2 gene fusion appears biologically distinct from other intraosseous SSRMS, following a course characterized by local recurrence with rare reports of metastasis to date.

Tenosynovial giant cell tumor-diffuse type, treated with a novel colony-stimulating factor inhibitor, pexidartinib: initial experience with MRI findings in three patients.

Tenosynovial giant cell tumor-diffuse type (diffuse TSGCT) is a benign but locally aggressive proliferative disorder of the synovium. Treatment is usually surgical, although in cases of extensive disease complete synovectomy is not possible and local recurrence rates are high. Pexidartinib (trade name Turalio®), a colony-stimulating factor-1 (CSF-1) inhibitor, was shown in a recent phase III trial to effectively treat diffuse TSGCT and is FDA approved for the treatment of adult patients with symptomatic diffuse TSGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) because of the risk of hepatotoxicity. Magnetic resonance imaging (MRI) is the preferred imaging modality for the diagnosis and surveillance of TSGCT. Here we present three patients with diffuse TSGCT of the knee who underwent multiple MRIs over several years while on pexidartinib. We describe the disease burden and signal characteristics on MRI and correlate with the response reported in the patients' medical records. Given that the use of pexidartinib and other CSF inhibitors is likely to increase, musculoskeletal radiologists should be aware of this novel non-operative treatment and the MRI appearance of diffuse TSGCT during therapy.

Percutaneous image-guided sternal biopsy: a cross-institutional retrospective review of diagnostic yield and safety in 50 cases.

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.

Pearls and Pitfalls for Soft-Tissue and Bone Biopsies: A Cross-Institutional Review.

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.

Radiographic parameter-driven decision tree reliably predicts aseptic mechanical failure of compressive osseointegration fixation.

Background and purpose - Compressive osseointegration fixation is an alternative to intramedullary fixation for endoprosthetic reconstruction. Mechanical failure of compressive osseointegration presents differently on radiographs than stemmed implants, therefore we aimed to develop a reliable radiographic method to determine stable integration.Patients and methods - 8 reviewers evaluated 11 radiographic parameters from 29 patients twice, 2 months apart. Interclass correlation coefficients (ICCs) were used to assess test-retest and inter-rater reliability. We constructed a fast and frugal decision tree using radiographic parameters with substantial test-retest agreement, and then tested using radiographs from a new cohort of 49 patients. The model's predictions were compared with clinical outcomes and a confusion matrix was generated.Results - 6 of 8 reviewers had non-significant intra-rater ICCs for ≥ one parameter; all inter-rater ICCs were highly reliable (p < 0.001). Change in length between the top of the spindle sleeve and bottom of the anchor plug (ICC 0.98), bone cortex hypertrophy (ICC 0.86), and bone pin hypertrophy (ICC 0.81) were used to create the decision tree. The sensitivity and specificity of the training cohort were 100% (95% CI 52-100) and 87% (CI 74-94) respectively. The decision tree demonstrated 100% (CI 40-100) sensitivity and 89% (CI 75-96) specificity with the test cohort.Interpretation - A stable spindle length and at least 3 cortices with bone hypertrophy at the implant interface predicts stable osseointegration; failure is predicted in the absence of bone hypertrophy at the implant interface if the pin sites show hypertrophy. Thus, our decision tree can guide clinicians as they follow patients with compressive osseo-integration implants.

Diffuse Idiopathic Skeletal Hyperostosis, Associated Morbidity, and Healthcare Utilization: A University Hospital Experience.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory condition affecting the spine, characterized by ossification of paravertebral ligaments. Our cross-sectional study investigated the frequency, associated morbidity, and healthcare utilization of DISH patients at our university hospital over 1 year. METHODS: Our university's database of spinal radiographs was searched from 2005 to 2015 for "DISH" or "diffuse idiopathic skeletal hyperostosis." The diagnosis of DISH was made by 2 board-certified radiologists (B.B. and C.Q.) based on the radiographs of cervical, thoracic, or lumbar spine. Patients from 2015 were further analyzed with regards to demographics, comorbidities, and healthcare interventions. Their spinal radiographs were reread by 2 authors. Patients were divided into those who fulfilled the Resnick criteria for DISH (group A), and those who did not fully meet the criteria but had radiographic features suggestive of DISH (group B). Means and proportions were used to describe variables. For group comparisons, t test and χ test were used. RESULTS: Between 2005 and 2015, 3439 radiology records mentioned DISH as a diagnosis. Of 195 patients diagnosed with DISH in 2015, 153 were in group A, 41 were in group B, and 2 had erroneous diagnoses. Chronic back pain was common, and more often reported in group B than in group A (81% vs 63%, p = 0.04). Substantial portions of patients required opioid medications for pain control (51%), spinal surgery (31%), and consultations with various specialists for regional pain (57%). CONCLUSIONS: Diffuse idiopathic skeletal hyperostosis is a diagnosis with significant morbidity, despite being commonly viewed as asymptomatic. A majority of DISH patients had chronic back pain, and a large proportion required spinal surgery, although there may be several confounders. Future research is needed to systematically assess healthcare utilization by DISH patients.

Implementing a comprehensive translational oncology platform: from molecular testing to actionability.

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.

CT-Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield.

PURPOSE: To evaluate the success rate of CT-guided bone biopsies in metastatic castration-resistant prostate cancer (mCRPC) and to investigate associated technical, imaging, and clinical parameters affecting diagnostic yields. MATERIALS AND METHODS: Eighty CT-guided bone biopsy specimens were obtained from 72 men (median age, 68 y; range, 49-89 y) enrolled in a multicenter trial to identify mechanisms of resistance in mCRPC. Successful biopsy was determined by histologic confirmation of tumor cells and successful isolation of RNA for molecular analysis. RESULTS: The overall success rate of CT-guided bone biopsies was 69% (55/80) based on histology and 64% (35/55) based on isolation of molecular material for RNA sequencing. Biopsies performed in lesions with areas of radiolucency had significantly higher diagnostic yields compared with lesions of predominantly dense sclerosis (95% vs 33%; P = .002) and lesions of predominantly subtle sclerosis (95% vs 65%; P = .04). Success rates increased in lesions with density ≤ 475 HU (79% for ≤ 475 HU vs 33% for > 475 HU; P = .001) and in lesions with ill-defined margins (76% for ill-defined margins vs 36% for well-circumscribed margins; P = .005). Alkaline phosphatase was the only clinical parameter to correlate significantly with diagnostic yield (83% for > 110 U/L vs 50% for ≤ 110 U/L; P = .001). CONCLUSIONS: Image-guided bone tumor biopsies can be successfully used to acquire cellular and molecular material for analyses in patients with osteoblastic prostate cancer metastases. Diagnostic yields are significantly increased in lesions with areas of radiolucency, density ≤ 475 HU, ill-defined margins, and interval growth and in patients with alkaline phosphatase > 110 U/L.

Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

Size-appropriate radiation doses in pediatric body CT: a study of regional community adoption in the United States.

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.

Clinical evaluation of a 31-year-old woman with crural monomelic amyotrophy.

This report describes the clinical presentation of a female patient diagnosed with crural MMA. Careful clinical correlation is necessary to distinguish crural MMA from other motor neuron diseases. When crural MMA is diagnosed, treatment options aim to alleviate symptoms.

Correlation Between Radiology ACGME Case Logs Values and ABR Core Exam Pass Rate.

RATIONALE AND OBJECTIVES: There is discordance between the American Board of Radiology (ABR) and many radiology trainees with respect to the most appropriate means to prepare for the ABR Core Examination. Whereas the ABR suggests that participation in routine clinical examination interpretation best prepares a trainee for the practical material of the test, residents, and many program directors feel that time away from clinical service for study and review courses are necessary. This study examines the relationship between studies interpreted in the first three years of residency as reported in the Accreditation Council for Graduate Medical Education case logs and performance of first-time test takers on the ABR Core Examination. MATERIALS AND METHODS: Accreditation Council for Graduate Medical Education case log data was anonymized for a single year cohort of residents in all accredited radiology residencies. This was then provided to the ABR and matched with performance on the Core Examination. A random effects logistic regression model was used to evaluate for a relationship between the number of examinations read and the pass/fail status of the Core Exam. RESULTS: Modeling using a linear and a quadratic term yields a significant relationship between case log values and Core Exam performance. There is a positive correlation until an inflection point of approximately 11,000 examinations, at which point a negative correlation develops. CONCLUSION: The data supports that active engagement in clinical duties is associated with better performance on the ABR Core Examination, with the caveat that there appears to be a point at which service outweighs educational value. Beyond this, performance on the examination declines.

Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a prospective study.

BACKGROUND: The Cochrane risk of bias tool is commonly criticized for having a low reliability. We aimed to investigate whether training of raters, with objective and standardized instructions on how to assess risk of bias, can improve the reliability of the Cochrane risk of bias tool. METHODS: In this pilot study, four raters inexperienced in risk of bias assessment were randomly allocated to minimal or intensive standardized training for risk of bias assessment of randomized trials of physical therapy treatments for patients with knee osteoarthritis pain. Two raters were experienced risk of bias assessors who served as reference. The primary outcome of our study was between-group reliability, defined as the agreement of the risk of bias assessments of inexperienced raters with the reference assessments of experienced raters. Consensus-based assessments were used for this purpose. The secondary outcome was within-group reliability, defined as the agreement of assessments within pairs of inexperienced raters. We calculated the chance-corrected weighted Kappa to quantify agreement within and between groups of raters for each of the domains of the risk of bias tool. RESULTS: A total of 56 trials were included in our analysis. The Kappa for the agreement of inexperienced raters with reference across items of the risk of bias tool ranged from 0.10 to 0.81 for the minimal training group and from 0.41 to 0.90 for the standardized training group. The Kappa values for the agreement within pairs of inexperienced raters across the items of the risk of bias tool ranged from 0 to 0.38 for the minimal training group and from 0.93 to 1 for the standardized training group. Between-group differences in Kappa for the agreement of inexperienced raters with reference always favored the standardized training group and was most pronounced for incomplete outcome data (difference in Kappa 0.52, p < 0.001) and allocation concealment (difference in Kappa 0.30, p = 0.004). CONCLUSIONS: Intensive, standardized training on risk of bias assessment may significantly improve the reliability of the Cochrane risk of bias tool.

Molecular Testing in Patients With Castration-Resistant Prostate Cancer and Its Impact on Clinical Decision Making.

PURPOSE: Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease. Many groups have performed mutational or immunohistochemistry (IHC) testing in metastatic CRPC to identify treatment targets. However, the frequency with which mutational or IHC data have an impact on clinical decision making and the outcomes of molecularly guided therapy in CRPC are largely unknown. We report our institution's experience with mutational and IHC testing in patients with metastatic CRPC and its impact on clinical decision making and patient outcomes. METHODS: Between 2012 and 2015, 59 patients with CRPC underwent metastatic tissue biopsies and were genotyped with a 37-cancer gene panel in a Clinical Laboratory Improvement Amendments-certified laboratory. PTEN expression by IHC testing was also measured in 35 of these samples. A retrospective chart review was performed to determine whether the genomic information was acted upon and the outcome of patients whose treatment was guided by molecular testing. RESULTS: Forty-six of 59 patients with CRPC (78.0%) had biopsies with adequate tumor for mutational testing. Thirty-one of 46 subjects (67.4%) had mutations identified by sequencing. Of the 35 patients with CRPC whose biopsies were evaluated for PTEN expression by IHC testing, 13 had PTEN loss. Two patients had treatment on the basis of molecular testing, and one of these subjects had greater tumor control with molecularly guided therapy than his immediate prior therapy. CONCLUSION: Targeted sequencing and IHC can identify clinically informative molecular abnormalities in CRPC. Despite this, a small minority of patients in our series underwent therapies guided by mutational or IHC testing. Actionability of abnormalities identified in metastatic CRPC may be improved with access to clinical trials, insurance approval for unapproved uses of existing anticancer drugs, and larger gene sequencing panels that include more frequently mutated genes.

Evaluation of Soft Tissue Sarcoma Response to Preoperative Chemoradiotherapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

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, Ktrans (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 Ktrans, ve (extravascular and extracellular volume fraction), and kep (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.

Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a study protocol.

BACKGROUND: The Cochrane risk of bias (RoB) tool has been widely embraced by the systematic review community, but several studies have reported that its reliability is low. We aim to investigate whether training of raters, including objective and standardized instructions on how to assess risk of bias, can improve the reliability of this tool. We describe the methods that will be used in this investigation and present an intensive standardized training package for risk of bias assessment that could be used by contributors to the Cochrane Collaboration and other reviewers. METHODS/DESIGN: This is a pilot study. We will first perform a systematic literature review to identify randomized clinical trials (RCTs) that will be used for risk of bias assessment. Using the identified RCTs, we will then do a randomized experiment, where raters will be allocated to two different training schemes: minimal training and intensive standardized training. We will calculate the chance-corrected weighted Kappa with 95% confidence intervals to quantify within- and between-group Kappa agreement for each of the domains of the risk of bias tool. To calculate between-group Kappa agreement, we will use risk of bias assessments from pairs of raters after resolution of disagreements. Between-group Kappa agreement will quantify the agreement between the risk of bias assessment of raters in the training groups and the risk of bias assessment of experienced raters. To compare agreement of raters under different training conditions, we will calculate differences between Kappa values with 95% confidence intervals. DISCUSSION: This study will investigate whether the reliability of the risk of bias tool can be improved by training raters using standardized instructions for risk of bias assessment. One group of inexperienced raters will receive intensive training on risk of bias assessment and the other will receive minimal training. By including a control group with minimal training, we will attempt to mimic what many review authors commonly have to do, that is-conduct risk of bias assessment in RCTs without much formal training or standardized instructions. If our results indicate that an intense standardized training does improve the reliability of the RoB tool, our study is likely to help improve the quality of risk of bias assessments, which is a central component of evidence synthesis.

Phase I trial of preoperative chemoradiation plus sorafenib for high-risk extremity soft tissue sarcomas with dynamic contrast-enhanced MRI correlates.

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.