Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma.

Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma. In this case report, we discuss the case of a patient with a EWSR1-NFATC2 fusion positive bone sarcoma who had exceptional tumor control through using pazopanib and surgery for an overall duration exceeding 5 years. We also review the literature on EWSR1-NFATC2 translocation-associated sarcomas and use of pazopanib in bone sarcomas.

A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

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.

Postchemotherapy Histiocyte-rich Pseudotumor Mimicking Residual Lymphoma: A Report of 11 Cases Correlating Clinicopathologic and Radiologic Findings.

Postchemotherapy histiocyte-rich pseudotumor is a rare event in lymphoma patients and can cause elevated metabolic activity on positron emission tomography-computed tomography scan mimicking residual tumor. Here, we reported 11 lymphoma cases showing mass-like lesions with increased fluorodeoxyglucose uptake after chemotherapy. These postchemotherapy lesions occurred in various anatomic sites including spleen, mediastinum, lymph node, and other tissue locations, concerning for refractory or residual lymphoma. Their median size was 2.7 cm (range, 1.4 to 7.7 cm) and the median standardized uptake value on positron emission tomography-computed tomography was 10.6 (range, 5.2 to 13.8). Histologic examination of these lesions demonstrated reactive changes mainly composed of histiocyte-rich proliferation without viable lymphoma. Fat necrosis, cholesterol cleft, and calcium deposit were also commonly observed. After biopsies, 3 patients received additional chemotherapy, 2 had stem cell transplant with adjuvant chemotherapy or radiation, 1 had surgical excision, and the remaining 5 patients did not receive any further treatment. Follow-up imaging studies showed the resolved or decreased fluorodeoxyglucose activities in all patients including those without additional treatments, consistent with benign/reactive nature of these pseudotumor lesions. This study illustrates postchemotherapy mass-like lesions with elevated metabolic activity do not always represent residual disease and provides awareness of correlation between radiologic and histologic features of these lesions to avoid misinterpretation and overtreatment of lymphoma patients after chemotherapy.

Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma.

The majority of patients with classical Hodgkin lymphoma (cHL) may be cured, but for patients with relapsed or refractory (R/R) cHL, the prognosis is unfavorable. Immune dysfunction is a significant contributor of relapse and a hallmark of cHL; in particular, the immune system is unable to eradicate lymphoma cells that overexpress immune checkpoint proteins. The blocking of this mechanism used by lymphoma cells to evade the immune system has resulted in clinical benefits. Use of checkpoint inhibitors (CPIs) in R/R cHL is associated with high response rates and an acceptable adverse effects profile. There is growing interest in combining chemotherapy with CPIs in frontline therapy of cHL treatment to improve relapse rates without significant additive toxicity. In this review, we discuss the current evidence supporting CPI use in R/R cHL and maintenance therapy. We present emerging CPI data in frontline adult cHL and assess its role in the elderly. In addition, we discuss critical immune-related toxicities and their management, and elaborate on the challenges of monitoring response and minimal residual disease as tools for maximizing efficacy by limiting toxicity.

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: New and future perspectives for parathyroid carcinoma.

This report summarizes published data on parathyroid cancer, with the inclusion of topics discussed at MEN2019: 16th International Workshop on Multiple Endocrine Neoplasia, 27-29 March 2019, Houston, TX, USA. An expert panel on parathyroid cancer was constituted by the Steering Committee to address key questions in the field. The objectives were to recap open forum discussion of interested parties from multiple disciplines. The expert panel met in a closed session to consult on the data to be highlighted on the evidence-based results and on the future directions. Preceding the Conference, members of the expert panel conducted an extensive literature search. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature. Questions were developed by the expert panel on parathyroid carcinoma. A comprehensive literature search for relevant studies was undertaken. This report represents the expert panel's synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of parathyroid carcinoma. This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of parathyroid carcinoma.

FDG PET/CT in Diagnosing COVID-19 Infection in a Cancer Patient With Exposure History But Minimal Symptoms.

A 56-year-old woman with high-grade neuroendocrine small cell carcinoma had known contact history of COVID-19 about 16 days prior to the restaging PET/CT. The patient was instructed to self-quarantine for 14 days, and no COVID-19 test was performed. Upon arrival, the patient had low-grade fever of 37.1°C, but did not meet infection control criteria for COVID-19 testing, and it was approved to proceed with PET/CT. The FDG PET/CT images revealed new multifocal hypermetabolic bilateral pulmonary ground-glass opacities that are suggestive of COVID-19 pneumonia. Meanwhile, the patient's symptoms worsened, and a blood test later confirmed COVID-19 infection.

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours.

OBJECTIVES: Localization of ectopic ACTH-secreting tumours causing Cushing syndrome (ECS) is essential for clinical management, yet often difficult. [68 Ga]-DOTATATE PET/CT ([68 Ga]-DOTA-(Tyr3 )-octreotate)] is an FDA-approved high-resolution diagnostic tool for imaging neuroendocrine tumours. Data on the clinical utility of [68 Ga]-DOTATATE in patients with ECS, however, are scarce. The objectives of this study were to determine the efficacy for ECS localization and the clinical benefit of [68 Ga]-DOTATATE imaging. METHOD: We conducted a retrospective review of all cases with ECS evaluated with [68 Ga]-DOTATATE from November 2016 through October 2018 at three referral centres. The clinical benefit of [68 Ga]-DOTATATE was based on detection of new tumours and resultant changes in management. RESULTS: Over the study period, 28 patients with ECS underwent [68 Ga]-DOTATATE: 17 for identification of the primary tumour and 11 during follow-up. [68 Ga]-DOTATATE identified the suspected primary ECS in 11/17 patients (65%). Of these, nine patients underwent surgery: eight with confirmed ECS (5 bronchial, 1 thymic, 1 pancreatic and 1 metastatic neuroendocrine tumour of unknown primary origin) and one patient with a false-positive scan (adrenal gland). Of the 11 patients with ECS who underwent [68 Ga]-DOTATATE evaluation during follow-up, the study led to changes in clinical management in 7/11 (64%) patients. CONCLUSIONS: [68 Ga]-DOTATATE is sensitive in detecting primary and metastatic ECS, often identifies occult tumours after conventional imaging, and impacts clinical care in the majority of patients.

American Head and Neck Society Endocrine Surgery Section update on parathyroid imaging for surgical candidates with primary hyperparathyroidism.

Health care consumer organizations and insurance companies increasingly are scrutinizing value when considering reimbursement policies for medical interventions. Recently, members of several American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) committees worked closely with one insurance company to refine reimbursement policies for preoperative localization imaging in patients undergoing surgery for primary hyperparathyroidism. This endeavor led to an AAO-HNS parathyroid imaging consensus statement (https://www.entnet.org/content/parathyroid-imaging). The American Head and Neck Society Endocrine Surgery Section gathered an expert panel of authors to delineate imaging options for preoperative evaluation of surgical candidates with primary hyperparathyroidism. We review herein the current literature for preoperative parathyroid localization imaging, with discussion of efficacy, cost, and overall value. We recommend that planar sestamibi imaging, single photon emission computed tomography (SPECT), SPECT/CT, CT neck/mediastinum with contrast, MRI, and four dimensional CT (4D-CT) may be used in conjunction with high-resolution neck ultrasound to preoperatively localize pathologic parathyroid glands. PubMed literature on parathyroid imaging was reviewed through February 1, 2019.

A PET Radiomics Model to Predict Refractory Mediastinal Hodgkin Lymphoma.

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUVmax). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

Correlation of fluorine 18-labeled sodium fluoride uptake and arterial calcification on whole-body PET/CT in cancer patients.

BACKGROUND: Fluorine-18-labeled sodium fluoride (F-NaF) uptake measured with PET in the vessel walls can indicate active microcalcification, a potential biomarker of higher-risk plaques, which are not indicated by macrocalcification measured with computed tomography (CT). The aim of this study was to determine the extent to which F-NaF uptake is correlated with calcification at arterial plaques in cancer patients undergoing whole-body PET/CT imaging. PATIENTS AND METHODS: Image data from 179 patients who underwent F-NaF PET/CT were evaluated retrospectively. Plaques were categorized into four groups by calcium score (CS) on CT: CS1 (≥1000); CS2 (400-999); CS3 (100-399), and CS4 (<100) and into three groups by F-NaF target-to-background ratio (TBR) on PET: TBRlow (≤1.0), TBRmedium (1.0-1.5), and TBRhigh (>1.5). Correlations between F-NaF uptake and CS were evaluated. RESULTS: Plaques with F-NaF uptake or arterial calcification were observed in 122 (76%) of the 179 patients. We found a weak but statistically significant positive correlation between CS and F-NaF uptake. The TBR in CS1 plaques was higher than those in CS3 and CS4 plaques, and the TBR in CS2 plaques was higher than that in CS3 plaques (P<0.05). Compared with patients whose plaques were with F-NaF uptake (TBR>1.5) or arterial calcification (CS>0), patients without plaques of F-NaF uptake or calcification were significantly younger (P=0.00) or with significantly more women (P=0.02). CONCLUSION: Our finding of a weak but significant positive correlation between F-NaF uptake and arterial calcification suggests that F-NaF PET/CT could provide complementary information of active microcalcification for atherosclerosis evaluation in cancer patients.

Positron emission tomography-computed tomography predictors of progression after DA-R-EPOCH for PMBCL.

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [18F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance (P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis (P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression.

Omitting cardiophrenic lymph nodes in the treatment of patients with Hodgkin lymphoma via modified involved-site radiation therapy.

Cardiophrenic lymph nodes (CPLNs) are occasionally involved in Hodgkin lymphoma (HL). We characterized the incidence of CPLN involvement among 169 HL patients and evaluated outcomes after treatment with omission of the CPLN region from the involved-site radiation therapy (ISRT) field. Three types of RT fields were used: standard (S)-ISRT, reduced-dose (RD)-ISRT (lower dose to CPLNs, standard to other sites), or modified (M)-ISRT (omission of CPLNs). CPLNs were involved at diagnosis in 29 patients (17%). Of the 20 patients who received RT after complete response to chemotherapy, 4(20%) received S-ISRT, 8(40%) RD-ISRT, and 8(40%) M-ISRT. The four-year progression-free survival was 94.7%. One relapse occurred at a non-CPLN site after RD-ISRT. The mean heart dose and volume of the heart that received 25 Gy was higher for S-ISRT patients compared to M-ISRT (p = .043 and p = .025, respectively). Re-planning the M-ISRT cases as S-ISRT resulted in significant increase in cardiac doses.

The diagnostic accuracy of neck ultrasound, 4D-Computed tomographyand sestamibi imaging in parathyroid carcinoma.

INTRODUCTION: Our aim was to investigate the accuracy of available imaging modalities for parathyroid carcinoma (PC) in our institution and to identify which imaging modality, or combination thereof, is optimal in preoperative determination of precise tumor location. METHODS: All operated PC patients in our institution between 2000 and 2015 that had at least one of the following in-house preoperative scans: neck ultrasonography (US), neck 4D-Computed Tomography (4DCT) and 99mTc Sestamibi SPECT/CT (MIBI). Sensitivity, specificity and accuracy of PC tumor localization were assessed individually and in combination. RESULTS: 20 patients fulfilled the inclusion criteria and were analysed. There were 18 US, 18 CT and 9 MIBI scans. The sensitivity and accuracy for tumor localisation of US was 80% (CI 56-94%) and 73% respectively, of 4DCT was 79% (CI 58-93%) and 82%, and of MIBI was 81% (CI 54-96%) and 78%. The sensitivity and accuracy of the combination of CT and MIBI was 94% (CI 73-100%) and 95% and for the combination of US, CT and MIBI was 100% (CI 72-100%) and 100% respectively. The wash-out of the PC lesions, expressed as a percentage change in Hounsfield Units from the arterial phase to early delayed phase was -9.29% and to the late delayed phase was -16.88% (n=11). CONCLUSIONS: The sensitivity of solitary preoperative imaging of PC patients, whether by US, CT or MIBI, is approximately 80%. Combinations of CT with MIBI and US increase the sensitivity to 95% or better. Combined preoperative imaging of patients with clinical possibility of PC is therefore recommended.

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.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Fat-Containing Hypermetabolic Masses on FDG PET/CT: A Spectrum of Benign and Malignant Conditions.

OBJECTIVE: This article focuses on identifying the imaging appearances of hypermetabolic fatty masses and masslike lesions on PET/CT and understanding the diagnostic challenges radiologists may face while interpreting findings of these lesions on PET/CT. This article provides an approach to aid in the diagnosis of these lesions and the appropriate management of patients. CONCLUSION: Both malignant and benign fat-containing masses and masslike lesions can show hypermetabolic activity on PET/CT. Although the differential diagnosis is broad, clinical history, anatomic location, and knowledge of anatomic variants and imaging features can help radiologists avoid misinterpretation of benign fatty lesions as malignancy.