Cancer Radiomic and Perfusion Imaging Automated Framework: Validation on Musculoskeletal Tumors.

PURPOSE: Limitations from commercial software applications prevent the implementation of a robust and cost-efficient high-throughput cancer imaging radiomic feature extraction and perfusion analysis workflow. This study aimed to develop and validate a cancer research computational solution using open-source software for vendor- and sequence-neutral high-throughput image processing and feature extraction. METHODS: The Cancer Radiomic and Perfusion Imaging (CARPI) automated framework is a Python-based software application that is vendor- and sequence-neutral. CARPI uses contour files generated using an application of the user's choice and performs automated radiomic feature extraction and perfusion analysis. This workflow solution was validated using two clinical data sets, one consisted of 40 pelvic chondrosarcomas and 42 sacral chordomas with a total of 82 patients, and a second data set consisted of 26 patients with undifferentiated pleomorphic sarcoma (UPS) imaged at multiple points during presurgical treatment. RESULTS: Three hundred sixteen volumetric contour files were processed using CARPI. The application automatically extracted 107 radiomic features from multiple magnetic resonance imaging sequences and seven semiquantitative perfusion parameters from time-intensity curves. Statistically significant differences (P < .00047) were found in 18 of 107 radiomic features in chordoma versus chondrosarcoma, including six first-order and 12 high-order features. In UPS postradiation, the apparent diffusion coefficient mean increased 41% in good responders (P = .0017), while firstorder_10Percentile (P = .0312) was statistically significant between good and partial/nonresponders. CONCLUSION: The CARPI processing of two clinical validation data sets confirmed the software application's ability to differentiate between different types of tumors and help predict patient response to treatment on the basis of radiomic features. Benchmark comparison with five similar open-source solutions demonstrated the advantages of CARPI in the automated perfusion feature extraction, relational database generation, and graphic report export features, although lacking a user-friendly graphical user interface and predictive model building.

An Approach to Undiagnosed Bone Tumors.

The radiographic appearance of primary bone tumors is important for initial diagnosis and often augments histopathological analysis. The original grading system relied on the radiographic analysis of the margin of the lesions to determine tumor aggression, which often corresponds with malignant potential. The recently developed, modified Lodwick-Madewell grading system also incorporates the appearance of lesion margins on radiographs but also considers the change in margins on serial radiographs and includes a category for clinically suspected, radiographically occult, aggressive lesions. This article reviews the prior and modified grading systems, and the concepts necessary for proper interpretation of the initial appearance of bone tumors which often determines the radiologist's recommendation for biopsy or follow-up imaging.

Bone Metastases: Mechanisms of the Metastatic Process, Imaging and Therapy.

The mechanisms by which tumors metastasize to bone are complex. Upon the successful establishment of metastatic deposits in the skeleton, detection of the disease becomes essential for therapeutic planning. The roles of CT, skeletal scintigraphy, SPECT/CT, MRI, PET/CT and PET/MRI will be reviewed. Therapeutic response criteria specifically designed to evaluate bone metastases (MD Anderson/MDA criteria) can guide image interpretation. Knowledge of therapeutic strategies such as systemic therapy with bisphosphonates or radiopharmaceuticals, radiation therapy, surgery, and percutaneous interventions such as vertebroplasty and radiofrequency ablation can help the radiologist produce reports that will provide maximum benefit to clinicians and patients.

Advanced Imaging in Musculoskeletal Oncology: Moving Away From RECIST and Embracing Advanced Bone and Soft Tissue Tumor Imaging (ABASTI) - Part I - Tumor Response Criteria and Established Functional Imaging Techniques.

According to the Revised Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the majority of bone metastases are considered to be nonmeasurable disease. Traditional response criteria rely on physical measurements. New criteria would be valuable if they incorporated newly developed imaging features in order to provide a more comprehensive assessment of oncological status. Advanced magnetic resonance imaging (MRI) sequences such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) with dynamic contrast-enhanced (DCE) perfusion imaging are reviewed in the context of the initial and post-therapeutic assessment of musculoskeletal tumors. Particular attention is directed to the pseudoprogression phenomenon in which a successfully treated tumor enlarges from the pretherapeutic baseline, followed by regression without a change in therapy.

Advanced Imaging in Musculoskeletal Oncology: Moving Away From RECIST and Embracing Advanced Bone and Soft Tissue Tumor Imaging (ABASTI)-Part II-Novel Functional Imaging Techniques.

Functional imaging can add valuable information to conventional imaging in the settings of tumor characterization and treatment response assessment. Traditional response criteria rely primarily on physical measurements, while functional imaging can potentially give a more comprehensive evaluation of oncological status. The second part of this review article discusses advanced imaging techniques such as susceptibility-weighted imaging, tumor-associated macrophage imaging, diffusion-weighted imaging, perfusion-weighted imaging, Dixon imaging, whole-body magnetic resonance imaging, whole-body low-dose dual energy computed tomography with virtual noncalcium technique, and ultrasound elastography.

Risks and Benefits of Gadolinium-Based Contrast-Enhanced MRI.

The responsible use of gadolinium-based contrast agents (GBCAs) requires a balance between safety and clinical utility. While nephrogenic systemic fibrosis (NSF) has been associated with most linear GBCAs few, if any, new cases have been verified since the successful implementation of screening programs to detect renal impairment and prevent susceptible patients from receiving these higher-risk agents. The likelihood of developing nephrogenic systemic fibrosis has been shown to be negligible with macrocyclic agents, prompting the American College of Radiology and other regulatory agencies to suggest that no screening is necessary when they are used. There is no solid evidence of negative clinical effect from the retention of macrocyclic agents in the brain while there is evidence that they wash out of the brain over time. GBCAs have many important clinical uses that can help prevent morbidity or death. This article reviews the risks and benefits of GBCA administration.

WITHDRAWN: Risks and Benefits of Gadolinium-Based Contrast Enhanced MRI.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in [Seminars in Ultrasound, CT, and MRI, 41/2 (2020) 170­182], https://dx.doi.org/10.1053/j.sult.2019.12.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal

Gadolinium-based Contrast Agents Improve Detection of Recurrent Soft-Tissue Sarcoma at MRI.

Purpose: To determine the diagnostic efficacy of gadolinium-based contrast agents for the detection of recurrent soft-tissue sarcoma compared with non-contrast-enhanced conventional MRI sequences. Materials and Methods: A retrospective study of patients with soft-tissue sarcomas who were imaged from January 2009 to December 2014 was performed. MRI studies from 69 patients (mean age, 61 years ± 15 [standard deviation], 45 men) with recurrent soft-tissue sarcoma and 63 age-, sex-, and tumor-matched controls with positive findings (nonrecurrence) were presented to six musculoskeletal radiologists at a tertiary cancer center in three image groupings. Group 1 consisted of precontrast T1-weighted and fat-suppressed T2-weighted images (no contrast agent). Group 2 consisted of precontrast and postcontrast fat-saturated T1-weighted images. Group 3 consisted of precontrast and fat-saturated postcontrast T1- and fat-suppressed T2-weighted images. Images within these three groups contained either recurrent soft-tissue sarcomas or positive postoperative findings (nonsarcoma). The presentation order of the first two image sets was reversed for half the readers. The readers were asked to classify presence of tumor on a five-point scale. The average score from the readers was used as consensus score for each case, and a case was considered positive if the average score was less than 3. Receiver operating characteristic (ROC) analysis was performed using the average score for each image set. Results: Assessment of the group 3 image set resulted in higher sensitivity (74%, 95% confidence interval [CI]: 62%, 83%) than the group 2 image set (64%, 95% CI: 51%, 75%), which was also more sensitive than the assessment of the group 1 images set (49%, 95% CI: 37%, 61%), with P = .02 for both. There was no significant difference in specificity between the three groups. The area under the ROC curve (AUC) for the assessment of group 1 was 0.78 (95% CI: 0.70, 0.86), which was significantly lower than that of group 2, 0.92 (95% CI: 0.87, 0.96) and group 3, 0.93 (95% CI: 0.88, 0.97), with P values of .0006 and < .0001, respectively. There was no difference between the AUCs of groups 2 and 3 (P = .58). Conclusion: Gadolinium-based contrast agents improved diagnostic performance in detection of recurrent soft-tissue sarcoma. Addition of fat-saturated T2-weighted images provided modest improvement in sensitivity.Keywords: Efficacy Studies, MR-Contrast Agent, Oncology, Soft Tissues/Skin© RSNA, 2020.

VIDEO: Preoperative CT Angiography for Scapula Osteocutaneous Free Flap Reconstructions.

OBJECTIVE. The objective of this video article is to discuss the use of the scapular osteocutaneous free flap in reconstructive procedures. We attempt to discuss normal and variant vascular anatomy, image acquisition via CT angiography, and image interpretation as well as computer-assisted design and manufacturing. CONCLUSION. The scapular osteocutaneous free flap is commonly used for maxillary and mandibular reconstructive surgery. The complex vasculature supplying the scapular region allows flap versatility. There are anatomic variations in the origin of the circumflex scapular and angular arteries. Our method of performing and reporting CT angiography for patients scheduled to undergo scapular osteocutaneous free flap procedures provides a reliable and reproducible means of communicating important elements of vasculature to surgeons. This in turn can facilitate the manufacturing of custom scapular cutting guides and improve surgical outcomes.

VIDEO: Preoperative CT Angiography for Fibular Free Flap Reconstructions.

OBJECTIVE: The objective of this video article is to provide an introduction to the use of fibular free flaps. Normal and variant vascular anatomy of the fibular free flap is discussed, as are imaging acquisition and CT angiography interpretation, computer-assisted design and manufacturing, and the limitations of the fibular free flap. CONCLUSION: The fibular free flap is commonly used for head and neck reconstructive surgery. Variation exists between individuals regarding the origin of the peroneal artery and the perforating arteries. Our method of performing CT angiography and reporting its findings for patients undergoing a fibular free flap procedure provides a reproducible means of identifying important elements of the vasculature and effectively communicating their locations to surgeons. Accurate communication can maximize the success of the flap harvesting and the preoperative manufacture of custom fibular cutting guides.

18F-FDG PET/CT as an Indicator of Survival in Ewing Sarcoma of Bone.

Objective: The existing literature of 18 F-FDG PET/CT in Ewing sarcoma investigates mixed populations of patients with both soft tissue and bone primary tumors. The aim of our study was to evaluate whether the maximum standardized uptake value (SUVmax) obtained with 18F-FDG PET/CT before and after induction chemotherapy can be used as an indicator of survival in patients with Ewing sarcoma originating exclusively in the skeleton. Materials and Methods: A retrospective database search from 2004-2011 identified 28 patients who underwent 18 F-FDG PET/CT before (SUV1, n= 28) and after (SUV2, n=23) induction chemotherapy. Mean follow up was 3.3 years and median follow up for survivors was 6.3 years (range: 2.6-9.8 years). Multivariate and univariate Cox proportional hazard model was used to assess for correlation of SUV1, SUV2, and the change in SUVmax with overall survival (OS) and progression-free survival (PFS). Results: Mean SUVmax was 10.74 before (SUV1) and after 4.11 (SUV2) induction chemotherapy. High SUV1 (HR = 1.05, 95% CI: 1.0-1.1, P = 0.01) and SUV2 (HR =1.2, 95% CI: 1.0-1.4, P = 0.01) were associated with worse OS. A cut off point of 11.6 was identified for SUV1. SUV1 higher than 11.6 had significantly worse OS (HR = 5.71, 95% CI: 1.85 - 17.61, P = 0.003) and PFS (HR = 3.16, 95% CI: 1.13 - 8.79, P = 0.03, P < 0.05 is significant). Conclusion: 18F-FDG PET/CT can be used as a prognostic indicator for survival in primary Ewing sarcoma of bone.

VIDEO: Preoperative CT Angiography for Anterolateral Thigh Flap Reconstructions.

OBJECTIVE: This video article will review the relevant vascular anatomy of the anterolateral thigh flap, describe the CT angiography (CTA) image acquisition, and describe how to report the locations of the perforating arteries along with characteristics that may be important to the surgeon. CONCLUSION: Our method of performing and reporting CTA for patients scheduled to undergo anterolateral thigh flap reconstruction provides a reproducible method of identifying perforating vessels and communicating their location to surgeons.

TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis.

PURPOSE: Osteoclast-mediated bone resorption through src kinase releases growth factors, sustaining bone metastases. This trial determined the recommended phase II dose (RP2D) and clinical efficacy of the src kinase inhibitor dasatinib combined with zoledronic acid in bone predominant, HER2-negative breast cancer metastases. EXPERIMENTAL DESIGN: A 3+3 lead in phase I design confirmed the RP2D allowing activation of the single-arm, phase II trial. Zoledronic acid was administered intravenously on day 1, and dasatinib was given orally once daily for 28 days each cycle as twice daily administration caused dose-limiting toxicity (DLT). Response was assessed every three cycles. N-telopeptide (NTx) was serially measured. RESULTS: A total of 25 patients were enrolled. No DLTs were noted at the RP2D of dasatinib = 100 mg/d. Common adverse events were grade 1-2: rash (9/25, 36%), fatigue (9/25, 36%), pain (9/25, 36%), nausea (6/25, 20%). The objective response rate in bone was 5/22 (23%), all partial responses (PR). The clinical benefit rate [PRs + stable disease (SD) ≥ 6 months] in bone was 8/22 (36%). Median time to treatment failure was 2.70 months [95% confidence interval (CI), 1.84-5.72] in the general cohort, 3.65 months (95% CI, 1.97-7.33) in patients with hormone receptor (HR)-positive breast cancer and 0.70 months (95% CI, 0.30-NA) in those with HR-negative disease. Factors associated with response in bone included lower tumor grade, HR-positive status, and pretreatment high NTx levels. CONCLUSIONS: Combination therapy was well tolerated and produced responses in bone in patients with HR-positive tumors. Clin Cancer Res; 22(23); 5706-12. ©2016 AACR.

Doxorubicin-Based Chemotherapy and Radiation Therapy Produces Favorable Outcomes in Limited-Stage Plasmablastic Lymphoma: A Single-Institution Review.

BACKGROUND: Plasmablastic lymphoma (PBL) is an aggressive variant of diffuse large B-cell lymphoma. We sought to assess the treatment outcomes after combined-modality therapy for early-stage PBL. MATERIALS AND METHODS: We retrospectively reviewed the outcomes of 10 consecutive patients diagnosed with stage I-II PBL from February 2001 to December 2013 at a single institution. The baseline clinical characteristics, treatment modalities, overall outcomes, and treatment-related toxicity were assessed. RESULTS: The median age at diagnosis was 50.5 years. All patients had extranodal disease; 2 were positive for human immunodeficiency virus. Seven patients received hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based chemotherapy, 2 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and 1 received dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin). Radiotherapy (RT) was administered after a complete response to chemotherapy in 7 patients and a partial response in 1 patient. At a median follow-up period of 42 months, the estimated 2-year progression-free and overall survival rates were 90% and 100%, respectively. CONCLUSION: PBL can be successfully treated with aggressive chemotherapy followed by RT. The treatment was well tolerated and can result in long-term survival for patients with limited-stage disease.

Single-institution experience in the treatment of primary mediastinal B cell lymphoma treated with immunochemotherapy in the setting of response assessment by 18fluorodeoxyglucose positron emission tomography.

PURPOSE: Excellent outcomes obtained after infusional dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (R-EPOCH) alone have led some to question the role of consolidative radiation therapy (RT) in the treatment of primary mediastinal B cell lymphoma (PMBL). We reviewed the outcomes in patients treated with 1 of 3 rituximab-containing regimens (cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone [R-HCVAD], or R-EPOCH) with or without RT. We also evaluated the ability of positron emission tomography-computed tomography (PET-CT) to identify patients at risk of relapse. METHODS AND MATERIALS: We retrospectively identified 97 patients with diagnoses of stage I/II PMBCL treated at our institution between 2001 and 2013. The clinical characteristics, treatment outcomes, and toxicity were assessed. We analyzed whether postchemotherapy PET-CT could identify patients at risk for progressive disease according to a 5 point scale (5PS) Deauville score assigned. RESULTS: Among 97 patients (median follow-up time, 57 months), the 5-year overall survival rate was 99%. Of patients treated with R-CHOP, 99% received RT; R-HCVAD, 82%; and R-EPOCH, 36%. Of 68 patients with evaluable end-of-chemotherapy PET-CT scans, 62% had a positive scan (avidity above that of the mediastinal blood pool [Deauville 5PS = 3]), but only 9 patients experienced relapse (n=1) or progressive disease (n=8), all with a 5PS of 4 to 5. Of the 25 patients who received R-EPOCH, 4 experienced progression, all with 5PS of 4 to 5; salvage therapy (RT and autologous stem cell transplantation) was successful in all cases. CONCLUSION: Combined modality immunochemotherapy and RT is well tolerated and effective for treatment of PMBCL. A postchemotherapy 5PS of 4 to 5, rather than 3 to 5, can identify patients at high risk of progression who should be considered for therapy beyond chemotherapy alone after R-EPOCH.

FDG PET/CT of primary bone tumors.

OBJECTIVE: Numerous primary bone tumors are encountered on (18)F-FDG PET/CT, and many are FDG avid. The degree of FDG uptake in bone tumors does not necessarily reflect malignant potential. In conjunction with radiographs, evaluation of morphologic characteristics on the CT portion of PET/CT scans is important for characterization of the lesions. FDG PET/CT has been found to be useful for staging and has also been found to reflect prognosis in some primary bone malignancies. The purpose of this article is to familiarize the reader with topics regarding FDG PET/CT and both malignant and benign primary bone tumors. CONCLUSION: FDG uptake alone is not adequate for characterizing primary bone tumors, and morphologic evaluation is an important factor in the interpretation of PET/CT scans. After diagnosis, FDG avidity and morphologic features can play an important role in staging and determining response to therapy. On completion of this article, readers should have an improved ability to evaluate the FDG uptake and CT morphologic features of malignant and benign primary bone tumors. Readers should also have a better understanding of the potential role of FDG PET/CT in the management of patients with osteosarcoma and Ewing sarcoma.

Differentiation of Benign Fluid Collections from Soft-Tissue Sarcomas on FDG-PET/CT.

OBJECTIVE: To assess the diagnostic performance of (18)F-FDG PET-CT in differentiating soft tissue sarcomas (STSs) from benign fluid collections (BFs). MATERIALS AND METHODS: Four readers independently reviewed 100 lesions on (18)F-FDG PET-CT and subjectively classified each lesion as an STS or BF and scored the spatial pattern of (18)F-FDG avidity (SP) of each on a 4-point ordered scale (thin, moderate, thick, solid). RESULTS: Subjective assessment by readers allowed sensitive (91%-98%) differentiation of STSs from BFs, with lower specificity (59%-91%). The STSs had significantly higher SUVmax (median 10.7, range: 2.0-33.7) than BFs (median 2.8, range: 1.1-12.3). Reader agreement in assessment of SP had average κ = 0.61 (range 0.46-0.70). Classification of thick or solid SP as STS yielded an inter-reader averaged sensitivity and specificity of 69% and 98%, respectively. The presence of thick or solid SP resulted in 14.1-fold increase in partial odds of STS. Each unit increase in SUVmax resulted in 1.35-fold increase in partial odds of STS. The receiver operating characteristic (ROC) curves and 95% intervals for SUVmax alone and SUVmax + SP overlapped. The average subjective assessments for the four readers and estimated performance of using SP alone were both contained within the 95% intervals of the two ROC curves. CONCLUSIONS: (18)F-FDG PET-CT is a sensitive modality for differentiating STSs from BFs. SUVmax and SP are significantly associated with STS. Classification schemes based upon SUVmax alone or augmented with SP can be useful for distinguishing STS from BF.