Publications by authors named "Marguerite T Parisi"

75 Publications

Pictorial Summary of Congenital Gallbladder and Biliary Duct Anomalies Presentation on HIDA Imaging.

Curr Probl Diagn Radiol 2021 Jan 9. Epub 2021 Jan 9.

Division of Nuclear Medicine, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC. Electronic address:

Hepatobiliary iminodiacetic acid (HIDA) scan is one of the principal imaging modalities for the evaluation of the gallbladder and biliary tree. Congenital biliary anomalies are rare and can be difficult to recognize on HIDA scan. They may also mimic other biliary pathology. The purpose of this article is to review the spectrum of congenital gallbladder and biliary anomalies and describe their imaging appearance on HIDA scan. In addition, the diagnostic utility of functional imaging with HIDA when evaluating biliary tract anomalies is described.
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http://dx.doi.org/10.1067/j.cpradiol.2020.12.009DOI Listing
January 2021

Metabolic response as assessed by F-fluorodeoxyglucose positron emission tomography-computed tomography does not predict outcome in patients with intermediate- or high-risk rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

Cancer Med 2021 Feb 19;10(3):857-866. Epub 2020 Dec 19.

Seattle Children's Hospital, Seattle, WA, USA.

Background: Strategies to optimize management in rhabdomyosarcoma (RMS) include risk stratification to assign therapy aiming to minimize treatment morbidity yet improve outcomes. This analysis evaluated the relationship between complete metabolic response (CMR) as assessed by F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET) imaging and event-free survival (EFS) in intermediate-risk (IR) and high-risk (HR) RMS patients.

Methods: FDG-PET imaging characteristics, including assessment of CMR and maximum standard uptake values (SUVmax) of the primary tumor, were evaluated by central review. Institutional reports of SUVmax were used when SUVmax values could not be determined by central review. One hundred and thirty IR and 105 HR patients had FDG-PET scans submitted for central review or had SUVmax data available from institutional report at any time point. A Cox proportional hazards regression model was used to evaluate the relationship between these parameters and EFS.

Results: SUVmax at study entry did not correlate with EFS for IR (p = 0.32) or HR (p = 0.86) patients. Compared to patients who did not achieve a CMR, EFS was not superior for IR patients who achieved a CMR at weeks 4 (p = 0.66) or 15 (p = 0.46), nor for HR patients who achieved CMR at week 6 (p = 0.75) or 19 (p = 0.28). Change in SUVmax at week 4 (p = 0.21) or 15 (p = 0.91) for IR patients or at week 6 (p = 0.75) or 19 (p = 0.61) for HR patients did not correlate with EFS.

Conclusion: Based on these data, FDG-PET does not appear to predict EFS in IR or HR-RMS. It remains to be determined whether FDG-PET has a role in predicting survival outcomes in other RMS subpopulations.
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http://dx.doi.org/10.1002/cam4.3667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897958PMC
February 2021

Questions and comments about 'Pediatric applications of Dotatate: early diagnostic and therapeutic experience'.

Pediatr Radiol 2021 Mar 11;51(3):495-496. Epub 2020 Nov 11.

Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

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http://dx.doi.org/10.1007/s00247-020-04872-1DOI Listing
March 2021

Management of Hydrocephalus in Children: Anatomic Imaging Appearances of CSF Shunts and Their Complications.

AJR Am J Roentgenol 2021 01 28;216(1):187-199. Epub 2020 Oct 28.

Department of Radiology, University of Washington School of Medicine, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA 98105.

This article addresses the management of hydrocephalus and the CSF shunts used to treat this entity. CSF shunts have a high failure rate. Imaging plays a pivotal role in assessing CSF shunt failure and determining the need for surgical revision. An in-depth knowledge of CSF shunt components, their failure modes, and the corresponding findings on anatomic imaging studies is necessary to ensure timely diagnosis and prevent permanent neurologic damage.
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http://dx.doi.org/10.2214/AJR.20.22888DOI Listing
January 2021

Complications of CSF Shunts in Pediatrics: Functional Assessment With CSF Shunt Scintigraphy-Performance and Interpretation.

AJR Am J Roentgenol 2020 12 21;215(6):1474-1489. Epub 2020 Oct 21.

Department of Radiology, University of Washington School of Medicine, Seattle Children's Hospital, 4800 Sand Point Way NE, Seattle, WA 98105.

The purpose of this article is to review the performance method and criteria for interpretation of CSF shunt scintigraphy studies. Interpretation of CSF shunt scintigraphy studies requires an in-depth understanding of hydrocephalus, the functioning of CSF shunts and their components, and the mechanisms of failure of such devices. Application of strict interpretive criteria when evaluating CSF shunt scintigraphy studies improves diagnostic yield, providing valuable functional information to the neurosurgical team who manages patients with shunted hydrocephalus.
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http://dx.doi.org/10.2214/AJR.20.22899DOI Listing
December 2020

Dual-energy X-ray absorptiometry bone densitometry in pediatrics: a practical review and update.

Pediatr Radiol 2021 Jan 28;51(1):25-39. Epub 2020 Aug 28.

Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.

The assessment of pediatric bone mineral content and density is an evolving field. In this manuscript we provide a practical review and update on the interpretation of dual-energy X-ray absorptiometry (DXA) in pediatrics including historical perspectives as well as a discussion of the recently published 2019 Official Position Statements of the International Society of Clinical Densitometry (ISCD) that apply to children.
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http://dx.doi.org/10.1007/s00247-020-04756-4DOI Listing
January 2021

Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial.

Lancet Oncol 2020 08 20;21(8):1110-1122. Epub 2020 Jul 20.

Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA.

Background: Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone.

Methods: In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02180867.

Findings: Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related.

Interpretation: In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up.

Funding: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.
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http://dx.doi.org/10.1016/S1470-2045(20)30325-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745646PMC
August 2020

PET with F-Fluorodeoxyglucose/Computed Tomography in the Management of Pediatric Sarcoma.

PET Clin 2020 Jul;15(3):333-347

Department of Radiology, Seattle Children's Hospital, M/S MA.7.220, 4800 Sand Point Way Northeast, Seattle, WA 98105, USA. Electronic address:

The role for PET with fludeoxyglucose F 18 (F-FDG PET)/computed tomography (CT) in the management of pediatric sarcomas continues to be controversial. The literature supports a role for PET/CT in the staging and surveillance of certain specific pediatric sarcoma subtypes; however, the data are less clear regarding whether PET/CT can be used as a biomarker for prognostication. Despite the interest in using this imaging modality in the management of pediatric sarcomas, most studies are limited by retrospective design and small sample size. Additional data are necessary to fully understand how best to use F-FDG PET/CT in pediatric sarcoma management.
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http://dx.doi.org/10.1016/j.cpet.2020.03.008DOI Listing
July 2020

You Can't Expect When You're Expecting: The Variable State of Parental Leave in Radiology Residency Programs.

Acad Radiol 2020 May 17. Epub 2020 May 17.

Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE. MA.7.220, Seattle, WA 98105.

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http://dx.doi.org/10.1016/j.acra.2020.04.013DOI Listing
May 2020

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group.

J Clin Oncol 2020 07 28;38(19):2160-2169. Epub 2020 Apr 28.

Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.

Purpose: The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF.

Patients And Methods: Patients were eligible at first relapse or first designation of refractory disease. Oral T and intravenous (IV) irinotecan were administered on days 1 to 5 of 21-day cycles. DIN was administered IV (days 2-5), and GM-CSF was administered subcutaneously (days 6-12). The primary end point was objective response, analyzed on an intent-to-treat basis per the International Neuroblastoma Response Criteria.

Results: Seventeen eligible patients were randomly assigned to I/T/DIN/GM-CSF (February 2013 to March 2015); 36 additional patients were nonrandomly assigned to I/T/DIN/GM-CSF (August 2016 to May 2017). Objective (complete or partial) responses were observed in nine (52.9%) of 17 randomly assigned patients (95% CI, 29.2% to 76.7%) and 13 (36.1%) of 36 expansion patients (95% CI, 20.4% to 51.8%). Objective responses were seen in 22 (41.5%) of 53 patients overall (95% CI, 28.2% to 54.8%); stable disease was also observed in 22 of 53. One-year progression-free and overall survival for all patients receiving I/T/DIN/GM-CSF were 67.9% ± 6.4% (95% CI, 55.4% to 80.5%) and 84.9% ± 4.9% (95% CI, 75.3% to 94.6%), respectively. Two patients did not receive protocol therapy and were evaluable for response but not toxicity. Common grade ≥ 3 toxicities were fever/infection (18 [35.3%] of 51), neutropenia (17 [33.3%] of 51), pain (15 [29.4%] of 51), and diarrhea (10 [19.6%] of 51). One patient met protocol-defined criteria for unacceptable toxicity (grade 4 hypoxia). Higher DIN trough levels were associated with response.

Conclusion: I/T/DIN/GM-CSF has significant antitumor activity in patients with relapsed/refractory neuroblastoma. Study of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers.
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http://dx.doi.org/10.1200/JCO.20.00203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325366PMC
July 2020

Correction to: Ovarian torsion: developing a machine-learned algorithm for diagnosis.

Pediatr Radiol 2020 May;50(5):757-758

Department of Radiology, Seattle Children's Hospital and the University of Washington, Seattle Children's Hospital, MA.7.220, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.

The original version of this paper included errors in Fig. 3. The corrected Fig. 3 is presented here.
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http://dx.doi.org/10.1007/s00247-020-04665-6DOI Listing
May 2020

Ovarian torsion: developing a machine-learned algorithm for diagnosis.

Pediatr Radiol 2020 05 22;50(5):706-714. Epub 2020 Jan 22.

Department of Radiology, Seattle Children's Hospital and the University of Washington, Seattle Children's Hospital, MA.7.220, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.

Background: Ovarian torsion is a common concern in girls presenting to emergency care with pelvic or abdominal pain. The diagnosis is challenging to make accurately and quickly, relying on a combination of physical exam, history and radiologic evaluation. Failure to establish the diagnosis in a timely fashion can result in irreversible ovarian ischemia with implications for future fertility. Ultrasound is the mainstay of evaluation for ovarian torsion in the pediatric population. However, even with a high index of suspicion, imaging features are not pathognomonic.

Objective: We sought to develop an algorithm to aid radiologists in diagnosing ovarian torsion using machine learning from sonographic features and to evaluate the frequency of each sonographic element.

Materials And Methods: All pediatric patients treated for ovarian torsion at a quaternary pediatric hospital over an 11-year period were identified by both an internal radiology database and hospital-based International Statistical Classification of Diseases and Related Health Problems (ICD) code review. Inclusion criteria were surgical confirmation of ovarian torsion and available imaging. Patients were excluded if the diagnosis could not be confirmed, no imaging was available for review, the ovary was not identified by imaging, or torsion involved other adnexal structures but spared the ovary. Data collection included: patient age; laterality of torsion; bilateral ovarian volumes; torsed ovarian position, i.e. whether medialized with respect to the mid-uterine line; presence or absence of Doppler signal within the torsed ovary; visualization of peripheral follicles; and presence of a mass or cyst, and free peritoneal fluid. Subsequently, we evaluated a non-torsed control cohort from April 2015 to May 2016. This cohort consisted of sequential girls and young adults presenting to the emergency department with abdominopelvic symptoms concerning for ovarian torsion but who were ultimately diagnosed otherwise. These features were then fed into supervised machine learning systems to identify and develop viable decision algorithms. We divided data into training and validation sets and assessed algorithm performance using sub-sets of the validation set.

Results: We identified 119 torsion-confirmed cases and 331 torsion-absent cases. Of the torsion-confirmed cases, significant imaging differences were evident for girls younger than 1 year; these girls were then excluded from analysis, and 99 pediatric patients older than 1 year were included in our study. Among these 99, all variables demonstrated statistically significant differences between the torsion-confirmed and torsion-absent groups with P-values <0.005. Using any single variable to identify torsion provided only modest detection performance, with areas under the curve (AUC) for medialization, peripheral follicles, and absence of Doppler flow of 0.76±0.16, 0.66±0.14 and 0.82±0.14, respectively. The best decision tree using a combination of variables yielded an AUC of 0.96±0.07 and required knowledge of the presence of intra-ovarian flow, peripheral follicles, the volume of both ovaries, and the presence of cysts or masses.

Conclusion: Based on the largest series of pediatric ovarian torsion in the literature to date, we quantified sonographic features and used machine learning to create an algorithm to identify the presence of ovarian torsion - an algorithm that performs better than simple approaches relying on single features. Although complex combinations using multiple-interaction models provide slightly better performance, a clinically pragmatic decision tree can be employed to detect torsion, providing sensitivity levels of 95±14% and specificity of 92±2%.
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http://dx.doi.org/10.1007/s00247-019-04601-3DOI Listing
May 2020

Initial treatment of pediatric differentiated thyroid cancer: a review of the current risk-adaptive approach.

Pediatr Radiol 2019 10 16;49(11):1391-1403. Epub 2019 Oct 16.

Department of Radiology, Emory University School of Medicine and Children's Healthcare of Atlanta at Egleston, Atlanta, GA, USA.

Differentiated thyroid cancer in children is a rare disease, accounting for only 1.4% of all pediatric malignancies. The diagnosis, biological behavior and treatment of differentiated thyroid cancer in children is different from that in adults. While there are many unresolved issues regarding approaches to management of differentiated thyroid cancer in the pediatric population, there is near universal consensus that treatment of this disease, which includes total thyroidectomy, central lymph node dissection at the time of initial surgery in those with nodal metastases, and the possible use of iodine-131 radiotherapy, is best performed by specialists including high-volume endocrine surgeons and experts with experience in calculating and administering radioactive iodine in children, when deemed appropriate.
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http://dx.doi.org/10.1007/s00247-019-04457-7DOI Listing
October 2019

Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Phase II Study.

Clin Cancer Res 2019 10 29;25(20):6044-6051. Epub 2019 Jul 29.

Departments of Pediatrics, Human Oncology and Genetics and the University of Wisconsin, Madison, Wisconsin.

Purpose: Combining anti-GD2 (disialoganglioside) mAb with GM-CSF, IL2, and isotretinoin is now FDA-approved for high-risk neuroblastoma minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in neuroblastoma and is more effective in neuroblastoma-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability, and antitumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to standard MRD therapy.

Patients And Methods: Hu14.18-IL2 was given at the recommended phase II dose of 12 mg/m/day on days 4-6 of a 28-day cycle with GM-CSF (250 mg/m/dose, days 1-2 and 8-14) and isotretinoin (160 mg/m/day, days 11-25). Tolerability was determined on the basis of the number of unacceptable toxicities observed. Response was evaluated separately for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients with disease evaluable only by I-metaiodobenzylguanidine (I-MIBG) scan and/or bone marrow histology (stratum 2).

Results: Fifty-two patients with recurrent or refractory neuroblastoma were enrolled; 51 were evaluable for toxicity and 45 were evaluable for response. Four patients had unacceptable toxicities, well below the protocol-defined rule for tolerability. Other grade 3 and 4 nonhematologic toxicities were expected and reversible. No responses were seen in stratum 1 ( = 14). In stratum 2 ( = 31), 5 objective responses were confirmed by central review (3 complete, 2 partial).

Conclusions: Hu14.18-IL2 given in combination with GM-CSF and isotretinoin is safe and tolerable. Patients with MIBG and/or bone marrow-only disease had a 16.1% response rate, confirming activity of the combination.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-0798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945765PMC
October 2019

Utility of 18F-FDG PET/CT in Infantile Myofibromatosis.

Clin Nucl Med 2019 Aug;44(8):676-679

From the Departments of Radiology.

Infantile myofibromatosis, a rare, nonmalignant disease seen almost exclusively in the pediatric population, can involve skin, muscle, soft tissues, bone, or viscera in either solitary or multicentric pattern. Although nonmalignant, visceral involvement in infantile myofibromatosis is a key prognostic indicator, which is associated with mortality in 75% of patients. Those with pulmonary involvement have a particularly poor outcome. This case illustrates the diagnostic utility of F-FDG PET/CT in defining disease extent in this unusual entity and compares it to other commonly used imaging modalities.
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http://dx.doi.org/10.1097/RLU.0000000000002627DOI Listing
August 2019

Role of the extent of prophylactic regional lymph node radiotherapy on survival in high-risk neuroblastoma: A report from the COG A3973 study.

Pediatr Blood Cancer 2019 07 9;66(7):e27736. Epub 2019 Apr 9.

Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts.

Purpose: Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary site irradiation and the extent of regional nodal coverage stratified by extent of surgical resection.

Methods: Three hundred thirty high-risk neuroblastoma patients with centrally reviewed radiotherapy plans were analyzed. Outcome was evaluated by the extent of nodal irradiation. For the 171 patients who also underwent surgery (centrally reviewed), outcome was likewise analyzed according to the extent of resection. Overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) were examined by Kaplan-Meier, log-rank test (EFS, OS), and Grey test (CILP).

Results: The five-year CILP, EFS, and OS for all 330 patients receiving radiotherapy on A3973 were 8.5% ± 1.5%, 47.2% ± 3.0%, and 59.7% ± 3.0%, respectively. There were no significant differences in outcomes based on the extent of lymph node irradiation regardless of the degree of surgical resection (< 90% or ≥90%).

Conclusion: Although local control remains a significant component of treatment of high-risk neuroblastoma, our results suggest there is no benefit of extensive lymph node irradiation, irrespective of the extent of surgical resection preceding stem cell transplant.
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http://dx.doi.org/10.1002/pbc.27736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281832PMC
July 2019

Pediatric Musculoskeletal Imaging: The Indications for and Applications of PET/Computed Tomography.

PET Clin 2019 Jan 24;14(1):145-174. Epub 2018 Oct 24.

Department of Diagnostic Imaging, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

The use of PET/computed tomography (CT) for the evaluation and management of children, adolescents, and young adults continues to expand. The principal tracer used is 18F-fluorodeoxyglucose and the principal indication is oncology, particularly musculoskeletal neoplasms. The purpose of this article is to review the common applications of PET/CT for imaging of musculoskeletal issues in pediatrics and to introduce the use of PET/CT for nononcologic issues, such as infectious/inflammatory disorders, and review the use of 18F-sodium fluoride in trauma and sports-related injuries.
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http://dx.doi.org/10.1016/j.cpet.2018.08.008DOI Listing
January 2019

Part-Time Pediatric Radiology: The Realities and Perceptions of Part-Time Employment in the Academic Setting.

AJR Am J Roentgenol 2018 11 14;211(5):971-977. Epub 2018 Aug 14.

1 All authors: Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, MA.7.220, 4800 Sandpoint Way NE, Seattle, WA 98105.

Objective: The goal of this study is to evaluate the perceptions held by full- and part-time academic pediatric radiologists with regard to the value of part-time radiologists, as well as the value placed on the work of part-time colleagues by their departments and institutions.

Materials And Methods: Two online surveys were distributed to full- and part-time pediatric radiologists via the Society for Pediatric Radiology e-mail list serve. Survey questions evaluated demographic data of both full- and part-time radiologists, as well as the perceptions each group has of part-time employment.

Results: Part-time radiologists reported significantly greater work-life balance than did their full-time counterparts and were less likely to report job dissatisfaction. Full- and part-time faculty have comparable levels of perceived departmental contributions. Part-time faculty were more likely to be younger women, early in their careers, and older men nearing retirement.

Conclusion: Part-time employment provides perceived benefits of increased work-life balance and job satisfaction and is viewed favorably by both full- and part-time radiologists in academic settings.
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http://dx.doi.org/10.2214/AJR.18.19922DOI Listing
November 2018

Two signs indicative of successful access in nuclear medicine cerebrospinal fluid diversionary shunt studies.

Pediatr Radiol 2018 08 8;48(8):1130-1138. Epub 2018 May 8.

Department of Radiology, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA.

Background: Successful shunt access is the first step in a properly performed nuclear medicine cerebrospinal fluid (CSF) shunt study.

Objective: To determine the significance of the radiotracer configuration at the injection site during initial nuclear medicine CSF shunt imaging and the lack of early systemic radiotracer activity as predictors of successful shunt access.

Materials And Methods: With Institutional Review Board approval, three nuclear medicine physicians performed a retrospective review of all consecutive CSF shunt studies performed in children at our institution in 2015. Antecedent nuclear medicine CSF shunt studies in these patients were also assessed and included in the review. The appearance of the reservoir site immediately after radiotracer injection was classified as either figure-of-eight or round/ovoid configuration. The presence or absence of early systemic distribution of the tracer on the 5-min static images was noted and separately evaluated.

Results: A total of 98 nuclear medicine ventriculoperitoneal CSF shunt studies were evaluated. Figure-of-eight configuration was identified in 87% of studies and, when present, had 93% sensitivity, 78% specificity, 92% accuracy, 98% positive predictive value (PPV) and 54% negative predictive value (NPV) as a predictor of successful shunt access. Early systemic activity was absent in 89 of 98 studies. Lack of early systemic distribution of the radiotracer had 98% sensitivity, 78% specificity, 96% accuracy, 98% PPV and 78% NPV as a predictor of successful shunt access. Figure-of-eight configuration in conjunction with the absence of early systemic tracer activity had 99% PPV for successful shunt access.

Conclusion: Figure-of-eight configuration at the injection site or lack of early systemic radiotracer activity had moderate specificity for successful shunt access. Specificity and PPV significantly improved when both signs were combined in assessment.
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http://dx.doi.org/10.1007/s00247-018-4150-8DOI Listing
August 2018

Clinical and Radiographic Response of Extramedullary Leukemia in Patients Treated With Gemtuzumab Ozogamicin.

J Pediatr Hematol Oncol 2019 Apr;41(3):e174-e176

Departments of Pediatrics.

Extramedullary leukemia (EML) is common in pediatric acute leukemia and can present at diagnosis or relapse. CD33 is detected on the surface of myeloid blasts in many patients with acute myelogenous leukemia and is the target of the antibody drug conjugate gemtuzumab ozogamicin (GO). Here we present 2 patients with CD33 EML treated with GO. They achieved significant response, with reduction of EML on both clinical and radiographic exams, specifically fluorine fluorodeoxyglucose positron emission tomography/computed tomography, demonstrating potential for targeted therapy with GO as a means of treating EML in patients with CD33 leukemia and the utility of fluorine fluorodeoxyglucose positron emission tomography/computed tomography monitoring in EML.
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http://dx.doi.org/10.1097/MPH.0000000000001201DOI Listing
April 2019

Radionuclide Imaging of Infection and Inflammation in Children: a Review.

Semin Nucl Med 2018 03 28;48(2):148-165. Epub 2017 Nov 28.

Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN.

With the exception of radiolabeled monoclonal antibodies, antibody fragments and radiolabeled peptides which have seen little application in the pediatric population, the nuclear medicine imaging procedures used in the evaluation of infection and inflammation are the same for both adults and children. These procedures include (1) either a two- or a three-phase bone scan using technetium-99m methylene diphosphonate; (2) Gallium 67-citrate; (3) in vitro radiolabeled white blood cell imaging (using Indium-oxine or Technetium hexamethyl-propylene-amine-oxime-labeled white blood cells); and (4) hybrid imaging with F-FDG. But children are not just small adults. Not only are the disease processes encountered in children different from those in adults, but there are developmental variants that can mimic, but should not be confused with, pathology. This article discusses some of the differences between adults and children with osteomyelitis, illustrates several of the common developmental variants that can mimic disease, and, finally, focuses on the increasing use of F-FDG PET/CT in the diagnosis and response monitoring of children with infectious and inflammatory processes. The value of and need for pediatric specific imaging protocols are reviewed.
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http://dx.doi.org/10.1053/j.semnuclmed.2017.11.002DOI Listing
March 2018

The Pediatric Patella: Normal Development, Anatomical Variants and Malformations, Stability, Imaging, and Injury Patterns.

Semin Musculoskelet Radiol 2018 Feb 6;22(1):81-94. Epub 2018 Feb 6.

Department of Radiology, University of Washington, Seattle, Washington.

We discuss the pediatric patella, with an emphasis on diagnostic imaging. Topics include normal patellar development, anatomical variants and their physiologic significance, genetic syndromes that alter the appearance of the patella, physiology of patellar tracking and stability, patellofemoral instability, and injury patterns and classification. Recognition of appropriate development on imaging prevents diagnostic error and unnecessary evaluation. Knowledge of the pertinent features of syndromes associated with morphological patellar abnormalities can aid in generating a succinct and relevant differential diagnosis. In patellofemoral instability, the patient's baseline anatomy, factors that predispose to instability, and the specific injuries that occur as a result are critical considerations for determining the course of treatment. Patellar sleeve fractures are unique to pediatric patients, and timely identification is critical to achieving an optimal treatment outcome.
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http://dx.doi.org/10.1055/s-0037-1608004DOI Listing
February 2018

Nuclear Medicine Applications in Pediatric Musculoskeletal Diseases: The Added Value of Hybrid Imaging.

Semin Musculoskelet Radiol 2018 Feb 6;22(1):25-45. Epub 2018 Feb 6.

Departments of Radiology, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington.

The introduction of diphosphonates in the 1970s revolutionized not only nuclear medicine but musculoskeletal imaging as well, providing functional assessment of entities such as osteomyelitis, trauma, and osseous metastatic disease. Although rarely the first-line imaging modality used today, nuclear medicine procedures continue to play a pivotal role in the evaluation of musculoskeletal diseases in children, providing whole-body assessment of disease involvement. More recently, the introduction of technologies such as single-photon emission computed tomography/computed tomography (SPECT/CT), as well as newer positron-emitting tracers such as fluorine-fluorodeoxyglucose and sodium F-fluorine, particularly when combined with CT (positron emission tomography/CT), have injected new life into the older established techniques and expanded the application of nuclear medicine imaging into new arenas. This article discusses the utility of standard nuclear medicine procedures as they apply to children with musculoskeletal disorders, focusing on the added value of and indications for SPECT/CT. Subsequently, we discuss the expanding role of positron-emitting agents in infection, trauma, and for the diagnosis, staging, and therapeutic response monitoring of children with malignant bone and soft tissue tumors. Differences between disease processes encountered in children as compared with adults are discussed; developmental variants that can, but should not, be confused with disease are illustrated. The need for pediatric-specific protocols is addressed.
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http://dx.doi.org/10.1055/s-0037-1615782DOI Listing
February 2018

Intraoperative Doppler sonogram in pediatric liver transplants: a pictorial review of intraoperative and early postoperative complications.

Pediatr Radiol 2018 03 22;48(3):401-410. Epub 2017 Dec 22.

Department of Radiology, Seattle Children's Hospital, University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA, 98105, USA.

A spectrum of vascular complications can be seen in pediatric liver transplant patients, including occlusion and hemodynamically significant narrowing of the vessels that provide inflow to or outflow from the graft. Intraoperative Doppler ultrasound (US) has the potential benefit of identifying vascular complications in pediatric liver transplant patients prior to abdominal closure. Importantly, intraoperative Doppler US can be used as a problem-solving tool in situations such as position-dependent kinking of the portal or hepatic veins, or in suspected vasospasm of the hepatic artery. Furthermore, this technique can be used for real-time reassessment after surgical correction of vascular complications. This pictorial review of intraoperative Doppler US in pediatric liver transplant patients illustrates normal findings and common vascular complications, including examples after surgical correction, in the perioperative period.
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http://dx.doi.org/10.1007/s00247-017-4053-0DOI Listing
March 2018

Validation of the mIBG skeletal SIOPEN scoring method in two independent high-risk neuroblastoma populations: the SIOPEN/HR-NBL1 and COG-A3973 trials.

Eur J Nucl Med Mol Imaging 2018 Feb 23;45(2):292-305. Epub 2017 Sep 23.

Institute of Radiology, Clinique de La Source, Lausanne, Switzerland.

Background: Validation of the prognostic value of the SIOPEN mIBG skeletal scoring system in two independent stage 4, mIBG avid, high-risk neuroblastoma populations.

Results: The semi-quantitative SIOPEN score evaluates skeletal meta-iodobenzylguanidine (mIBG) uptake on a 0-6 scale in 12 anatomical regions. Evaluable mIBG scans from 216 COG-A3973 and 341 SIOPEN/HR-NBL1 trial patients were reviewed pre- and post-induction chemotherapy. The prognostic value of skeletal scores for 5-year event free survival (5 yr.-EFS) was tested in the source and validation cohorts. At diagnosis, both cohorts showed a gradual non-linear increase in risk with cumulative scores. Several approaches were explored to test the relationship between score and EFS. Ultimately, a cutoff score of ≤3 was the most useful predictor across trials. A SIOPEN score ≤ 3 pre-induction was found in 15% SIOPEN patients and in 22% of COG patients and increased post-induction to 60% in SIOPEN patients and to 73% in COG patients. Baseline 5 yr.-EFS rates in the SIOPEN/HR-NBL1 cohort for scores ≤3 were 47% ± 7% versus 26% ± 3% for higher scores at diagnosis (p < 0.007) and 36% ± 4% versus 14% ± 4% (p < 0.001) for scores obtained post-induction. The COG-A3973 showed 5 yr.-EFS rates for scores ≤3 of 51% ± 7% versus 34% ± 4% for higher scores (p < 0.001) at diagnosis and 43% ± 5% versus 16% ± 6% (p = 0.004) for post-induction scores. Hazard ratios (HR) significantly favoured patients with scores ≤3 after adjustment for age and MYCN-amplification. Optimal outcomes were recorded in patients who achieved complete skeletal response.

Conclusions: Validation in two independent cohorts confirms the prognostic value of the SIOPEN skeletal score. In particular, patients with an absolute SIOPEN score > 3 after induction have very poor outcomes and should be considered for alternative therapeutic strategies.
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http://dx.doi.org/10.1007/s00259-017-3829-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747549PMC
February 2018

ACR-SPR-STR Practice Parameter for the Performance of Cardiac Positron Emission Tomography - Computed Tomography (PET/CT) Imaging.

Clin Nucl Med 2017 Dec;42(12):918-927

From the *UT Southwestern Medical Center, Dallas, TX; †Baptist Hospital of Miami, Miami, FL; ‡Mayo Clinic, Rochester, MN; §University of Washington, Seattle, WA; ∥Lenox Hill Radiology, New York, NY; ¶MD Anderson, Houston, TX; **University of Pennsylvania; and ††Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.

This clinical practice parameter has been developed collaboratively by the American College of Radiology (ACR), the Society for Pediatric Radiology (SPR), and the Society of Thoracic Radiology (STR). This document is intended to act as a guide for physicians performing and interpreting positron emission tomography-computed tomography (PET/CT) of cardiac diseases in adults and children. The primary value of cardiac PET/CT imaging include evaluation of perfusion, function, viability, inflammation, anatomy, and risk stratification for cardiac-related events such as myocardial infarction and death. Optimum utility of cardiac PET/CT is achieved when images are interpreted in conjunction with clinical information and laboratory data. Measurement of myocardial blood flow, coronary flow reserve and detection of balanced ischemia are significant advantages of cardiac PET perfusion studies. Increasingly cardiac PET/CT is used in diagnosis and treatment response assessment for cardiac sarcoidosis.
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http://dx.doi.org/10.1097/RLU.0000000000001827DOI Listing
December 2017

Validation of Postinduction Curie Scores in High-Risk Neuroblastoma: A Children's Oncology Group and SIOPEN Group Report on SIOPEN/HR-NBL1.

J Nucl Med 2018 03 8;59(3):502-508. Epub 2017 Sep 8.

Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, California.

A semiquantitative I-metaiodobenzylguanidine (I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children's Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. A retrospective analysis of I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited I-MIBG-avid, International Neuroblastoma Staging System stage 4 neuroblastoma. I-MIBG scans were evaluated at 2 time points, diagnosis ( = 345) and postinduction ( = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0-3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% [CS ≤ 12] vs. 21.4% ± 3.6% [CS > 12], < 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% [CS ≤ 2] vs. 16.4% ± 4.2% [CS > 2], < 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and gene copy number. The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.
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http://dx.doi.org/10.2967/jnumed.117.195883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868501PMC
March 2018

Pediatric Abdominal Radiographs: Common and Less Common Errors.

AJR Am J Roentgenol 2017 Aug 7;209(2):417-429. Epub 2017 Jun 7.

1 Department of Radiology, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, MA.7.220, Seattle, WA 98105.

Objective: Interpretation of abdominal radiographs of children benefits from a firm knowledge of the congenital anomalies and pathologies unique to this patient population, leveraged by a systematic approach. Interpretive errors place the patients and their families at risk for a delay in diagnosis, unnecessary additional imaging, a potential increase in the radiation burden, and possible psychologic trauma.

Conclusion: In this article, we describe the common and uncommon potential pitfalls in pediatric abdominal radiography, using several of our own interpretive errors as a framework while providing teaching points to help avoid these mistakes.
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http://dx.doi.org/10.2214/AJR.17.17889DOI Listing
August 2017

Vaginal Ewing Sarcoma: An Uncommon Clinical Entity in Pediatric Patients.

J Clin Imaging Sci 2017 25;7:17. Epub 2017 Apr 25.

Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Ewing sarcoma, including classical Ewing sarcoma of the bone and primitive neuroectodermal tumors arising in bone or extraosseous primary sites, is a highly aggressive childhood neoplasm. We present two cases of Ewing sarcoma arising from the vagina in young girls. Previously reported cases in literature focused on their pathologic rather than radiographic features. We describe the spectrum of multimodality imaging appearances of Ewing sarcoma at this unusual primary site. Awareness of vaginal Ewing tumors may facilitate prompt diagnosis and lead to a different surgical approach than the more commonly encountered vaginal rhabdomyosarcoma.
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http://dx.doi.org/10.4103/jcis.JCIS_96_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433652PMC
April 2017

Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial.

Lancet Oncol 2017 07 23;18(7):946-957. Epub 2017 May 23.

Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma.

Methods: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis. Patients of any age were eligible at first designation of relapse or progression, or first designation of refractory disease, provided organ function requirements were met. Patients previously treated for refractory or relapsed disease were ineligible. Computer-based randomisation with sequence generation defined by permuted block randomisation (block size two) was used to randomly assign patients (1:1) to irinotecan and temozolomide plus either temsirolimus or dinutuximab, stratified by disease category, previous exposure to anti-GD2 antibody therapy, and tumour MYCN amplification status. Patients in both groups received oral temozolomide (100 mg/m per dose) and intravenous irinotecan (50 mg/m per dose) on days 1-5 of 21-day cycles. Patients in the temsirolimus group also received intravenous temsirolimus (35 mg/m per dose) on days 1 and 8, whereas those in the dinutuximab group received intravenous dinutuximab (17·5 mg/m per day or 25 mg/m per day) on days 2-5 plus granulocyte macrophage colony-stimulating factor (250 μg/m per dose) subcutaneously on days 6-12. Patients were given up to a maximum of 17 cycles of treatment. The primary endpoint was the proportion of patients achieving an objective (complete or partial) response by central review after six cycles of treatment, analysed by intention to treat. Patients, families, and those administering treatment were aware of group assignment. This study is registered with ClinicalTrials.gov, number NCT01767194, and follow-up of the initial cohort is ongoing.

Findings: Between Feb 22, 2013, and March 23, 2015, 36 patients from 27 COG member institutions were enrolled on this groupwide study. One patient was ineligible (alanine aminotransferase concentration was above the required range). Of the remaining 35 patients, 18 were randomly assigned to irinotecan-temozolomide-temsirolimus and 17 to irinotecan-temozolomide-dinutuximab. Median follow-up was 1·26 years (IQR 0·68-1·61) among all eligible participants. Of the 18 patients assigned to irinotecan-temozolomide-temsirolimus, one patient (6%; 95% CI 0·0-16·1) achieved a partial response. Of the 17 patients assigned to irinotecan-temozolomide-dinutuximab, nine (53%; 95% CI 29·2-76·7) had objective responses, including four partial responses and five complete responses. The most common grade 3 or worse adverse events in the temsirolimus group were neutropenia (eight [44%] of 18 patients), anaemia (six [33%]), thrombocytopenia (five [28%]), increased alanine aminotransferase (five [28%]), and hypokalaemia (four [22%]). One of the 17 patients assigned to the dinutuximab group refused treatment after randomisation; the most common grade 3 or worse adverse events in the remaining 16 patients evaluable for safety were pain (seven [44%] of 16), hypokalaemia (six [38%]), neutropenia (four [25%]), thrombocytopenia (four [25%]), anaemia (four [25%]), fever and infection (four [25%]), and hypoxia (four [25%]); one patient had grade 4 hypoxia related to therapy that met protocol-defined criteria for unacceptable toxicity. No deaths attributed to protocol therapy occurred.

Interpretation: Irinotecan-temozolomide-dinutuximab met protocol-defined criteria for selection as the combination meriting further study whereas irinotecan-temozolomide-temsirolimus did not. Irinotecan-temozolomide-dinutuximab shows notable anti-tumour activity in patients with relapsed or refractory neuroblastoma. Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen.

Funding: National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(17)30355-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527694PMC
July 2017